Review
Immunohistochemistry in the distinction between
Department of Pathology,
Belfast Health and Social Care
Trust, Belfast, Northern Ireland
Correspondence to
Professor W Glenn McCluggage,
Department of Pathology, Royal
Group of Hospitals Trust,
Grosvenor Road, Belfast BT12
6BA, Northern Ireland;
glenn.mccluggage@
belfasttrust.hscni.net
Accepted 27 June 2011
Published Online First
18 July 2011
596
primary and metastatic ovarian mucinous neoplasms
W Glenn McCluggage
ABSTRACT
The distinction between a primary and metastatic
mucinous carcinoma within the ovary may be
problematic. In most cases, the distinction can be made
by careful pathological examination encompassing both
the gross and microscopic findings and taking into
account the distribution of the disease. However,
immunohistochemistry may be of value in certain
scenarios. In this review, I discuss the value of markers
in the distinction between primary ovarian mucinous
neoplasms and metastatic mucinous carcinomas from
the colorectum, appendix, pancreas, biliary tract,
stomach and cervix, the most common primary sites
which give rise to metastatic mucinous carcinoma within
the ovary. There is a significant degree of
immunophenotypic overlap between primary ovarian
mucinous neoplasms and metastatic mucinous
carcinomas from the gastrointestinal tract, especially the
upper gastrointestinal type; this is because most primary
ovarian mucinous carcinomas and borderline tumours are
of so-called intestinal or enteric type and exhibit some
degree of positivity with enteric markers. Mullerian type
primary ovarian mucinous neoplasms also exist and
exhibit distinct immunohistochemical differences to the
more common intestinal type.
INTRODUCTION
Although traditionally regarded as the second most
common type of primary ovarian carcinoma
following serous carcinoma, recent studies have
illustrated that primary ovarian mucinous carci-
nomas are rather uncommon neoplasms repre-
senting approximately 3% of primary malignant
ovarian epithelial tumours.1 2 Although some of the
differences in prevalence between older and recent
studies may be explained by different criteria used
to distinguish between a mucinous borderline
tumour at the upper end of the spectrum and
a well-differentiated mucinous carcinoma with
expansile invasion,3e5 the main reason for the
decrease in incidence is that previously many
metastatic mucinous carcinomas in the ovary were
probably misinterpreted as primary ovarian
neoplasms; clinical, gross and microscopic patho-
logical features suggestive of a metastatic mucinous
carcinoma in the ovary are discussed elsewhere in
this issue. One point I wish to make is that
although metastatic mucinous carcinomas in the
ovary are still sometimes misdiagnosed as
a primary ovarian mucinous carcinoma or even
a mucinous borderline tumour due to the
pronounced maturation effect seen with some
secondary mucinous carcinomas in the ovary, we
have to some extent come full circle in that, in my
opinion, there is now a tendency to overplay the
possibility of a secondary mucinous carcinoma even
when the pathological features are obviously those
of a primary ovarian neoplasm. I consider that in
a large majority of cases, the distinction between
a primary and a secondary mucinous carcinoma in
the ovary can be achieved by careful pathological
examination encompassing both the gross and
microscopic findings and taking into account the
distribution of the disease. It has been stated that
when a mucinous carcinoma is diagnosed in the
ovary, further investigations, such as colonoscopy
and detailed imaging of the upper abdomen, should
be undertaken to exclude a primary neoplasm
elsewhere. I feel this is unnecessary in most cases
since, as discussed, basic pathological examination
is usually sufficient to distinguish between
a primary and a secondary ovarian mucinous
neoplasm.
Carcinomas arising in a wide range of primary
sites may metastasise to the ovary; in this review, I
largely restrict my comments to metastatic
adenocarcinomas with abundant intracytoplasmic
mucin, the so-called mucinous carcinomas. Meta-
static carcinomas that do not typically contain
significant intracytoplasmic mucin, such as breast
carcinoma, are not discussed. Metastatic mucinous
carcinomas in the ovary may be from a number of
primary sites, chiefly including the colorectum,
pancreas, biliary tract, appendix, stomach and
cervix.6e8 If there is no known history of a primary
neoplasm elsewhere (or even if there is), the likeli-
hood of the ovary or one of the aforementioned
sites being the primary site is largely initially
formulated on the basis of the morphological
features, as discussed elsewhere in this issue.
However, immunohistochemistry may be of
considerable assistance (table 1). The markers
discussed may also be useful in helping to ascertain
the primary site of a disseminated mucinous
carcinoma. It is worth pointing out that a large
majority of primary ovarian mucinous carcinomas
are unilateral and stage 1 (confined to the ovary) at
presentation.9 10 Therefore, a disseminated
mucinous carcinoma in a woman is unlikely to be
of ovarian origin.
At this point, I stress that most primary ovarian
mucinous carcinomas (and borderline tumours) are
of the so-called intestinal or enteric type (discussed
in the next section). These intestinal-type
neoplasms are almost invariably negative with
oestrogen receptor (ER), progesterone receptor (PR)
and WT1 and are almost always CA125 negative.9
Hormone receptor negativity means that ER and
PR are of no value in distinguishing between
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Table 1 Typical immunophenotype of mucinous carcinomas of various organs
CK7 CK20
Intestinal-type ovarian D or F F or D
Mullerian-type ovarian D N
Colorectal (including appendix) N* D D
Pancreatic D or F N or F
Biliary D or F N or F
Gastric D or F N or F
Cervical D N or F
These represent the most typical immunostaining patterns but aberrant staining may occur in individual neoplasms.
*Rectal adenocarcinomas may be CK7 positive.
yNon-HPV-related cervical adenocarcinomas may be p16 negative.
CEA, carcinoembryonic antigen; D, diffusely positive; ER, oestrogen receptor; F, focally positive; HPV, human papillomavirus; N, negative.
a primary and a secondary ovarian mucinous neoplasm. Recent
studies have shown that a proportion of primary ovarian
mucinous carcinomas overexpress HER2 and exhibit HER2
amplification.11 A response to trastuzumab therapy has been
shown in a small number of cases of recurrent ovarian mucinous
carcinomas11 and future studies are warranted to assess the
value of targeted therapies in this setting.
METASTATIC COLORECTAL ADENOCARCINOMA
The most definitive use of immunohistochemistry in the
distinction between a primary and a secondary mucinous
carcinoma in the ovary is in helping to confirm or exclude
a colorectal metastasis. However, most metastatic colorectal
adenocarcinomas within the ovary, although they contain some
intracytoplasmic mucin, are not overtly mucinous and more
closely resemble a primary ovarian endometrioid than
a mucinous carcinoma, a so-called pseudoendometrioid appear-
ance.12 Features in favour of a primary ovarian endometrioid
adenocarcinoma include the presence of an adenofibromatous
growth pattern, squamous elements or endometriosis, this triad
being characteristic of primary ovarian endometrioid neoplasms.
Features in favour of a colorectal metastasis include the presence
of dirty or segmental necrosis, an absence of the triad described
and more significant nuclear atypia compared with the degree of
glandular differentiation than seen in endometrioid adenocarci-
nomas. However, there may be morphological overlap, and in
this diagnostic scenario, immunohistochemistry is almost
definitive. The so-called differential cytokeratin (CK7 and CK20)
staining can be used along with CA125, ER, carcinoembryonic
antigen (CEA) and CDX2. Primary ovarian endometrioid
adenocarcinomas are usually diffusely positive with CK7, CA125
and ER and negative with CK20, CEA and CDX213e24 (some
primary ovarian endometrioid adenocarcinomas exhibit focal
nuclear staining with CDX2 and squamous morules within
these neoplasms are commonly diffusely positive25 26). By
contrast, metastatic colorectal adenocarcinomas with a pseu-
doendometrioid appearance are usually diffusely positive with
CK20, CEA and CDX2 and negative with CK7, CA125 and ER.
CEA staining is sometimes difficult to interpret since there is
typically staining of necrotic material and inflammatory cells
such that it may be problematic to assess staining in the tumour
cells.
In the distinction between a primary ovarian mucinous
neoplasm (borderline or carcinoma) and those metastatic colo-
rectal adenocarcinomas with an overt mucinous appearance,
immunohistochemistry is less useful, although it may be
helpful. As stated, most primary ovarian mucinous carcinomas
and borderline tumours are of the so-called intestinal or enteric
type.3e5 They are very commonly positive with the enteric
J Clin Pathol 2012;65:596e600. doi:10.1136/jcp.2010.085688
Review
CEA CA19.9 CDX2 CA125 ER DPC4 p16
F or D D F N N D N
N N or F N D D D N
D D N N D N or F
D or F D F F or D N D or N N
D or F D F F or D N D or N N
D or F D F N N D N
D or F N N or F D N or F D Dy
markers CK20, CEA, CA19.9 and CDX2. CA19.9 is often
diffusely positive while CK20, CEA and CDX2 are most
commonly focally positive but may be negative or diffusely
reactive such that in an individual case they may not assist due
to overlap. Positivity with these markers may be reflected in
increased serum levels of CEA and especially CA19.9 in primary
ovarian mucinous neoplasms. For example, it has been shown
that the serum CA19.9 may be massively elevated in primary
ovarian mucinous neoplasms of intestinal type and that these
levels are of no value in predicting whether a suspected ovarian
mucinous neoplasm is benign, borderline or malignant.27 Help-
fully, primary ovarian mucinous neoplasms of intestinal type are
usually, although not always, diffusely CK7 positive, even when
they exhibit staining with the enteric markers listed; as such, the
distribution of CK7 and CK20 staining is more important than
absolute positive or negative staining. Although most colorectal
carcinomas, including those with an overt mucinous appearance,
are CK7 negative or very focally positive, it should be borne in
mind that rectal carcinomas are more likely to be CK7 positive
than those at other sites in the large intestine28 29 and this is
a potential pitfall. In one study, 74% of rectal adenocarcinomas
were CK7 positive.28 Additionally, poorly differentiated colo-
rectal adenocarcinomas may exhibit aberrant staining and are
more likely to exhibit some degree of CK7 positivity than better
differentiated neoplasms.18 30 It can be summarised that
although immunohistochemistry may be useful, there is some
degree of immunophenotypic overlap between primary ovarian
mucinous carcinomas and borderline tumours of intestinal type
and metastatic colorectal adenocarcinomas with a mucinous
appearance.
A number of other markers such as villin, a-methylacyl-CoA
racemase, meprin a, guanylyl cyclase C, MUC2, dipeptidase 1
and b-catenin have been reported to be of value since they are
more likely to be expressed in colorectal than primary ovarian
carcinomas31e36; some of these markers were chosen for
immunohistochemical analysis after gene expression profiling
showed them to be unregulated in colorectal adenocarcinomas
compared with ovarian mucinous carcinomas.32 36 37 However,
due to intestinal differentiation in primary ovarian mucinous
neoplasms, there is considerable immunophenotypic overlap and
these markers, most of which are not in widespread use, may
not be of value in an individual case. In one study of primary
ovarian mucinous and metastatic colorectal carcinomas, 83% of
metastatic colorectal carcinomas exhibited nuclear positivity
with b-catenin while only 9% of primary ovarian mucinous
carcinomas did so.31 It should be noted that ovarian endome-
trioid adenocarcinomas may exhibit nuclear b-catenin positivity,
especially within the squamous morules; this is secondary to
b-catenin gene mutation.38
597
 Review
SOME PRIMARY OVARIAN MUCINOUS NEOPLASMS ARE OF
TERATOMATOUS ORIGIN AND EXHIBIT AN OVERT LARGE
INTESTINAL IMMUNOPHENOTYPE
A small proportion of primary ovarian mucinous neoplasms of
intestinal type are of teratomatous origin.39 40 Although other
teratomatous elements are often present on microscopic exam-
ination, in some cases they are overgrown by the mucinous
neoplasm. Some of these tumours exhibit a similar immuno-
profile to the usual primary ovarian mucinous neoplasms of
intestinal type in that they are diffusely CK7 and CA19.9
positive and focally positive with CK20, CEA and CDX2 (these
may represent upper gastrointestinal-type mucinous neoplasms
arising in a teratoma); others exhibit an overt large intestinal
immunophenotype being negative with CK7 and diffusely
positive with CK20, CEA and CDX2.
METASTATIC APPENDICEAL NEOPLASMS
Immunohistochemical studies have been instrumental in
establishing that in most cases of pseudomyxoma peritonei
(PMP), the appendix is the site of primary neoplasm, with the
low-grade mucinous epithelium within the appendiceal, ovarian,
omental and peritoneal lesions being positive with the intestinal
markers CK20, CEA, CDX2 and MUC2 and usually negative
with CK7.41e45 One exception is that primary ovarian mucinous
neoplasms arising in teratomas and exhibiting an overt large
intestinal immunophenotype may uncommonly give rise to
PMP40; it seems to be overt large intestinal-type mucinous
epithelium with a low-grade cytology, which has the capacity to
give rise to PMP.
Outside the setting of PMP, metastatic appendiceal adeno-
carcinomas within the ovary may be composed of signet ring
cells and small mucinous glands and closely mimic a metastatic
gastric adenocarcinoma rather than the more usual colorectal
adenocarcinoma.46 It is my experience that with such
morphology, the appendix is often overlooked or not considered
as a likely site of primary neoplasm. In this scenario, immuno-
histochemistry is useful in that if the neoplasm is diffusely
positive with CK20, CEA and CDX2 and negative with CK7,
this is suggestive of a metastatic appendiceal rather than gastric
adenocarcinoma.
METASTATIC PANCREATIC, BILIARY TRACT AND GASTRIC
ADENOCARCINOMAS
A relatively uncommon, but sometimes problematic, area is the
distinction between a metastatic pancreatic or biliary tract
mucinous carcinoma within the ovary and a primary ovarian
mucinous carcinoma or borderline tumour.47 The immunophe-
notype of pancreatic and biliary tract carcinomas will be
discussed together since these are similar. There is considerable
immunophenotypic overlap between primary ovarian mucinous
neoplasms of intestinal type and metastatic pancreatic or biliary
tract mucinous carcinomas in that these neoplasms are most
commonly diffusely positive with CK7 and CA19.9 and they
may be negative, diffusely or focally positive with CK20, CEA
and CDX2. It is doubtful whether any marker, at present, can
reliably distinguish between a primary ovarian intestinal-type
mucinous neoplasm and a metastatic pancreatic or biliary tract
mucinous carcinoma since the former, on the basis of histo-
chemical, immunohistochemical and ultrastructural studies, has
been shown to contain pancreatic, biliary or gastric-type mucins
(especially gastric type), which can collectively be referred to as
upper gastrointestinal-type mucins.48 However, some markers
may be of value. In my experience, pancreatic and biliary tract
598
carcinomas are often CA125 positive49 50 and this may be useful
in that most primary ovarian mucinous neoplasms of intestinal
type are negative or at the most focally positive.9 Therefore, any
appreciable CA125 staining in a mucinous neoplasm is against
a primary ovarian carcinoma (an exception is primary ovarian
Mullerian-type mucinous neoplasms, which may be CA125
positiveddiscussed later) and more in keeping with a pancreatic
or biliary tract carcinoma. However, we have recently noticed an
unusual phenomenon in that recurrent or metastatic primary
ovarian mucinous carcinomas of intestinal type may be CA125
positive, even when the primary neoplasm was negative.51 As
stated earlier, primary ovarian mucinous neoplasms of intestinal
type are almost invariably negative with ER, PR and WT1.
Pancreatic and biliary tract adenocarcinomas are also usually
negative with these markers,52 although I have noticed that
some pancreatic adenocarcinomas are focally PR positive. There
is often non-specific cytoplasmic staining of mucinous carci-
nomas with PR. On low-power examination, this may errone-
ously be misinterpreted as a positive reaction and high power is
required to confirm that the nuclei are negative. One marker
that may be of use in the distinction between a primary ovarian
mucinous neoplasm of intestinal type and a pancreatic or biliary
tract adenocarcinoma is DPC4 (deleted in pancreatic carcinoma
4, MADH4, SMAD4). This is almost invariably positive in
primary ovarian mucinous neoplasms while approximately 50%
of pancreatic and some biliary tract adenocarcinomas are
negative.53e57 This is because this tumour suppressor gene on
chromosome 18q is genetically inactivated by allelic loss in
approximately 50% of pancreatic and in some biliary adenocar-
cinomas. However, DPC4 is not in widespread use. Other
markers that have been purported to be of use include meso-
thelin, fascin and prostate stem cell antigen since these are more
likely to be expressed in pancreatic than ovarian mucinous
carcinomas58; however, again there is overlap and these markers
are not in widespread use.
Other upper gastrointestinal tract carcinomas, such as gastric
carcinoma, when they metastasise to the ovary usually contain
signet ring cells and the overall morphological features, in most
cases, are not especially likely to be confused with a primary
ovarian mucinous neoplasm. The immunophenotype of gastric
carcinomas with regard to CK7, CK20, CA19.9, CEA, CA125 and
CDX2 is essentially similar to that of pancreatic and biliary tract
adenocarcinomas.
METASTATIC CERVICAL ADENOCARCINOMA
Metastatic cervical adenocarcinoma within the ovary may
mimic a primary ovarian mucinous or endometrioid neoplasm,
either borderline or malignant; in such cases, the cervical
primary may be extremely small or even not recognisably
invasive.59e61 p16 may be useful in that most cervical adeno-
carcinomas are diffusely positive due to the presence of high-risk
human papillomavirus (HPV) while most, but not all, primary
ovarian mucinous and endometrioid neoplasms are negative or
focally positive.62e64 More useful than p16 immunohistochem-
istry are molecular studies (PCR or in situ hybridisation) to
demonstrate HPV, the presence of which is virtually diagnostic
of a cervical primary. However, it should be remembered that
unusual morphological types of primary cervical adenocarci-
nomas may be HPV negative, including overt mucinous
neoplasms such as adenoma malignum.65 In the distinction
between a primary ovarian endometrioid neoplasm and a meta-
static cervical adenocarcinoma, ER and CEA are useful in that
primary ovarian endometrioid neoplasms are usually ER positive
and CEA negative while the converse applies to metastatic
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cervical adenocarcinomas. These markers are not useful in the
distinction between a primary ovarian mucinous neoplasm of
intestinal type and a metastatic cervical adenocarcinoma in that
both tumour types are usually ER negative and often CEA
positive.
IMMUNOPHENOTYPE OF PRIMARY OVARIAN MULLERIAN-TYPE
MUCINOUS NEOPLASMS
In discussing the immunophenotype of primary ovarian
mucinous neoplasms, I have so far restricted my comments to
those of intestinal or enteric type, by far the most common type
of primary ovarian mucinous carcinomas and borderline
tumours. A Mullerian- or endocervical-type primary ovarian
mucinous neoplasm also exists; borderline variants are
uncommon and carcinomas rare.66 The immunophenotype of
ovarian Mullerian mucinous neoplasms has not been extensively
investigated, and studies have mainly concentrated on borderline
tumours, but there are distinct immunohistochemical differ-
ences between intestinal- and Mullerian-type mucinous
neoplasms.67 68 Both are typically diffusely positive with CK7,
although, as stated, intestinal-type neoplasms may be only
focally positive or even negative on rare occasions. As discussed,
the intestinal-type tumours typically express, focally or
diffusely, enteric markers such as CK20, CEA, CA19.9 and
CDX2. Mullerian-type mucinous neoplasms are usually negative
with these markers (although they may be positive with CA19.9
and squamous elements, which can be present in these
neoplasms, may be CEA positive) but typically express
Mullerian markers, such as CA125, ER and PR. WT1 is usually
negative. CA125, ER and PR are usually negative in intestinal-
type mucinous neoplasms. One study described the presence of
reserve cell-like cells, morphologically similar to reserve cells in
the cervix, in Mullerian mucinous borderline tumours; similar to
cervical reserve cells, these cells are positive with p63, 34bE12
and CK17.69
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.
REFERENCES
1. Seidman JD, Horkayne-Szakaly I, Haiba M, et al. The histologic type and stage
distribution of ovarian carcinomas of surface epithelial origin. Int J Gynecol Pathol
2004;23:41e4.
2. Köbel M, Kalloger SE, Huntsman DG, et al; Cheryl Brown Ovarian Cancer Outcomes
Unit of the British Columbia Cancer Agency. Differences in tumor type in low-stage
versus high-stage ovarian carcinomas. Int J Gynecol Pathol 2010;29:203e11.
3. Hart WR. Mucinous tumors of the ovary: a review. Int J Gynecol Pathol
2005;24:4e25.
4. McCluggage WG. My approach to and thoughts on typing of ovarian carcinomas. J
Clin Pathol 2008;61:152e63.
5. Lerwill MF, Young RH. Mucinous tumours of the ovary. Diagn Histopathol
2008;14:366e87.
6. McCluggage WG, Wilkinson N. Metastatic neoplasms involving the ovary: a review
with an emphasis on morphological and immunohistochemical features.
Histopathology 2005;47:231e47.
7. Lee KR, Young RH. The distinction between primary and secondary mucinous
carcinomas of the ovary: gross and histologic findings in 50 cases. Am J Surg Pathol
2003;27:281e92.
8. Seidman JD, Kurman RJ, Ronnett BM. Primary and metastatic mucinous
adenocarcinomas in the ovary: incidence in routine practice with a new approach to
improve intraoperative diagnosis. Am J Surg Pathol 2003;27:985e93.
9. Tabrizi AD, Kalloger SE, Kobel M, et al. Primary ovarian mucinous carcinoma of
intestinal type: significance of pattern of invasion and immunohistochemical
expression profile in a series of 31 cases. Int J Gynecol Pathol 2010;29:99e107.
10. Chiesa AG, Deavers MT, Veras E, et al. Ovarian intestinal type mucinous borderline
tumors: are we ready for a nomenclature change? Int J Gynecol Pathol
2010;29:108e12.
11. McAlpine JN, Wiegand KC, Vang R, et al. HER2 overexpression and amplification is
present in a subset of ovarian mucinous carcinomas and can be targeted with
trastuzumab therapy. BMC Cancer 2009;9:433.
J Clin Pathol 2012;65:596e600. doi:10.1136/jcp.2010.085688
Review
12. Lewis MR, Deavers MT, Silva EG, et al. Ovarian involvement by metastatic
colorectal adenocarcinoma: still a diagnostic challenge. Am J Surg Pathol
2006;30:177e84.
13. McCluggage WG. Recent advances in immunohistochemistry in the diagnosis of
ovarian neoplasms. J Clin Pathol 2000;53:558e60.
14. McCluggage WG. Recent advances in immunohistochemistry in gynaecological
pathology. Histopathology 2002;46:309e26.
15. McCluggage WG, Young RH. Immunohistochemistry as a diagnostic aid in the
evaluation of ovarian tumors. Semin Diagn Pathol 2005;22:3e32.
16. McCluggage WG. Immunohistochemical markers as a diagnostic aid in ovarian
pathology. Diagn Histopathol 2008;14:335e51.
17. Berezowski K, Stasny JF, Kornstein MJ. Cytokeratins 7 and 20 and
carcinoembryonic antigen in ovarian and colonic carcinoma. Mod Pathol
1996;9:1040e4.
18. Park SY, Kim HS, Hong EK, et al. Expression of cytokeratins 7 and 20 in primary
carcinomas of the stomach and colorectum and their value in the differential
diagnosis of metastatic carcinomas to the ovary. Hum Pathol 2002;33:1078e85.
19. Lagendijk JH, Mullink H, van Diest PJ, et al. Immunohistochemical differentiation
between primary adenocarcinomas of the ovary and ovarian metastases of colon and
breast origin. Comparison between a statistical and intuitive approach. J Clin Pathol
1999;52:283e90.
20. Raspollini MR, Amunni G, Villannucci A, et al. Utility of CDX-2 in distinguishing
between primary and secondary (intestinal) mucinous ovarian carcinoma. Appl
Immunohistochem Mol Morphol 2004;12:127e31.
21. Werling RW, Yaziji H, Bacchi CE, et al. CDX2, a highly sensitive and specific marker
of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476
primary and metastatic carcinomas. Am J Surg Pathol 2003;27:303e10.
22. Groisman GM, Meir A, Sabo E. The value of cdx2 immunostaining in differentiating
primary ovarian carcinomas from colonic carcinomas metastatic to the ovaries. Int J
Gynecol Pathol 2003;23:52e7.
23. Tornillo L, Moch H, Diener PA, et al. CDX-2 immunostaining in primary and
secondary ovarian carcinomas. J Clin Pathol 2004;57:641e3.
24. Vang R, Gown AM, Wu LS, et al. Immunohistochemical expression of CDX2 in
primary ovarian mucinous tumors and metastatic mucinous carcinomas involving the
ovary: comparison with CK20 and correlation with coordinate expression of CK7.
Mod Pathol 2006;19:1421e8.
25. Houghton O, Connolly LE, McCluggage WG. Morules in endometrioid proliferations
of the uterus and ovary consistently express the intestinal transcription factor CDX2.
Histopathology 2008;53:156e65.
26. Wani Y, Notochara K, Saegusa M, et al. Aberrant Cdx2 expression in endometrial
lesions with squamous differentiation: important role of Cdx2 in squamous morula
formation. Hum Pathol 2008;39:1072e9.
27. Kelly P, Archbold P, Price JH, et al. Serum CA19.9 levels are commonly elevated in
primary ovarian mucinous tumours but cannot be used to predict the histological
subtype. J Clin Pathol 2010;63:169e73.
28. Zhang PJ, Shah M, Spiegel GW, et al. Cytokeratin 7 immunoreactivity in rectal
adenocarcinomas. Appl Immunohistochem Mol Morphol 2003;11:306e10.
29. Saad RS, Silverman JF, Khalifa MA, et al. CDX2, cytokeratins 7 and 20
immunoreactivity in rectal adenocarcinoma. Appl Immunohistochem Mol Morphol
2009;17:196e201.
30. Kende AI, Carr NJ, Sobin LH. Expression of cytokeratins 7 and 20 in carcinomas of
the gastrointestinal tract. Histopathology 2003;42:137e40.
31. Chou YY, Jeng YM, Kao HL, et al. Differentiation of ovarian mucinous carcinoma and
metastatic colorectal adenocarcinoma by immunostaining with b-catenin.
Histopathology 2003;43:151e6.
32. Heinzelmann-Schwarz VA, Scolyer RA, Scurry JP, et al. Low meprin alpha
expression differentiates primary ovarian mucinous carcinoma form
gastrointestinal cancers that commonly metastasise to the ovary. J Clin Pathol
2007;60:622e6.
33. Ciocca V, Bombonati A, Palazzo JP, et al. Guanyl cyclase C is a specific marker for
differentiating primary and metastatic ovarian mucinous neoplasms. Histopathology
2009;55:182e8.
34. Logani S, Oliva E, Arnell PM, et al. Use of novel immunohistochemical markers
expressed in colonic adenocarcinoma to distinguish primary ovarian tumors from
metastatic colorectal carcinoma. Mod Pathol 2005;18:19e25.
35. Albarracin CT, Jafri J, Montag AG, et al. Differential expression of MUC2 and
MUC5AC mucin genes in primary ovarian and metastatic colonic carcinoma. Hum
Pathol 2000;31:672e7.
36. Okamoto T, Matsumura N, Mandai M, et al. Distinguishing primary from secondary
mucinous ovarian tumors: an algorithm using the novel marker DPEP1. Mod Pathol
2011;24:267e76.
37. Heinzelmann-Schwarz VA, Gardiner-Garden M, Henshall SM, et al. A distinct
molecular profile associated with mucinous epithelial ovarian cancer. Br J Cancer
2006;94:904e13.
38. Geyer GT, Lopez-Garcia MA, Sanchez-Estevez C, et al. Pathogenetic pathways in
ovarian endometrioid adenocarcinoma: a molecular study of 29 cases. Am J Surg
Pathol 2009;33:1157e63.
39. Vang R, Gown AM, Zhao C, et al. Ovarian mucinous tumors associated with mature
cystic teratomas: morphologic and immunohistochemical analysis identifies a subset
of potential teratomatous origin that shares features of lower gastrointestinal tract
mucinous tumors more commonly encountered as secondary tumors in the ovary.
Am J Surg Pathol 2007;31:854e69.
599
 Review
40. Ronnett BM, Seidman JD. Mucinous tumors arising in ovarian mature cystic
teratomas: relationship to the clinical syndrome of pseudomyxoma peritonei. Am J
Surg Pathol 2003;27:650e7.
41. Ronnett BM, Kurman RJ, Zahn CM, et al. Pseudomyxoma peritonei in women:
a clinicopathologic analysis of 30 cases with emphasis on site of origin, prognosis,
and relationship to ovarian mucinous tumors of low malignant potential. Hum Pathol
1995;26:509e24.
42. Ronnett BM, Zahn CM, Kurman RJ, et al. Disseminated peritoneal
adenomucinosis and peritoneal mucinous carcinomatosis: a clinicopathologic analysis
of 109 cases with emphasis on distinguishing pathologic features, site of origin,
prognosis and relationship to “pseudomyxoma peritonei”. Am J Surg Pathol
1995;19:1390e408.
43. Ronnett BM, Shmookler BM, Diener-West M, et al. Immunohistochemical evidence
supporting the appendiceal origin of pseudomyxoma peritonei in women. Int J
Gynecol Pathol 1997;16:1e9.
44. Guerrieri C, Franlund B, Boeryd B. Expression of cytokeratin 7 in simultaneous
mucinous tumors of the ovary and appendix. Mod Pathol 1995;8:573e6.
45. O’Connell JT, Hacker CM, Barsky SH. MUC2 is a molecular marker for
pseudomyxoma peritonei. Mod Pathol 2002;15:958e72.
46. Ronnett BM, Kurman RJ, Shmookler BM, et al. The morphologic spectrum of
ovarian metastases of appendiceal adenocarcinomas: a clinicopathologic and
immunohistochemical analysis of tumors often misinterpreted as primary ovarian
tumors or metastatic tumors from other gastrointestinal sites. Am J Surg Pathol
1997;21:1144e55.
47. Young RH, Scully RE. Ovarian metastases from carcinoma of the gallbladder and
extrahepatic bile ducts simulating primary tumors of the ovary: a report of six cases.
Int J Gynecol Pathol 1990;9:60e72.
48. Tenti P, Aguzzi A, Riva C, et al. Ovarian mucinous tumors frequently express markers
of gastric, intestinal and pancreaticobiliary epithelial cells. Cancer 1992;69:2131e42.
49. Tempero M, Takasaki H, Uchida E, et al. Co-expression of CA19.9, DU-PAN-2,
CA125 and TAG-72 in pancreatic adenocarcinoma. Am J Surg Pathol 1989;13(Suppl
1):89e95.
50. Han L, Pansare V, Al-Abbadi M, et al. Combination of MUC5AC and WT-1
immunohistochemistry is useful in distinguishing pancreatic ductal carcinoma from
ovarian serous carcinoma in effusion cytology. Diagn Cytopathol 2010;38:333e6.
51. Miller K, Millar J, McCluggage WG. Emergence of CA125 immunoreactivity in
recurrent or metastatic primary ovarian mucinous neoplasms of intestinal type. Am J
Surg Pathol (In press).
52. Goldstein NS, Bassi D, Uzieblo A. WT1 is an integral component of an antibody
panel to distinguish pancreaticobiliary and some ovarian epithelial neoplasms. Am J
Clin Pathol 2001;116:246e52.
53. Ji H, Isacson C, Seidman JD, et al. Cytokeratins 7 and 20, Dpc4 and MUC5AC in the
distinction of metastatic mucinous carcinomas in the ovary from primary ovarian
mucinous carcinomas: Dpc4 assists in identifying metastatic pancreatic carcinomas.
Int J Gynecol Pathol 2002;21:391e400.
54. Tascilar M, Offerhaus GJ, Altink R, et al. Immunohistochemical labelling for the
Dpc4 gene product is a specific marker for adenocarcinoma in biopsy specimens
from the pancreas and bile duct. Am J Clin Pathol 2001;116:831e7.
600
55. Argani P, Shaukat A, Kaushal M, et al. Differing rates of loss of DPC4 expression and
of p53 overexpression among carcinomas of the proximal and distal bile ducts.
Cancer 2001;19:1332e41.
56. Schutte M, Hruban RH, Hedrick L, et al. DPC4 gene in various tumor types. Cancer
Res 1996;56:2527e30.
57. Wilentz RE, Su GH, Dai JL, et al. Immunohistochemical labelling for dpc4 mirrors
genetic status in pancreatic adenocarcinomas: a new marker of DPC4 inactivation.
Am J Pathol 2000;156:37e43.
58. Cao D, Ji H, Ronnett BM. Expression of mesothelin, fascin, and prostate stem cell
antigen in primary ovarian mucinous tumors and their use in differentiating primary
ovarian mucinous tumors from metastatic pancreatic mucinous carcinomas in the
ovary. Int J Gynecol Pathol 2005;24:67e72.
59. Ronnett BM, Yemelyanova AV, Vang R, et al. Endocervical adenocarcinomas with
ovarian metastases: analysis of 29 cases with emphasis on minimally invasive
cervical tumors and the ability of the metastases to simulate primary ovarian
neoplasms. Am J Surg Pathol 2008;32:1835e53.
60. Elishaev E, Gilks CB, Miller D, et al. Synchronous and metachronous endocervical
and ovarian neoplasms: evidence supporting interpretation of the ovarian neoplasms
as metastatic endocervical adenocarcinomas simulating primary ovarian surface
epithelial neoplasms. Am J Surg Pathol 2005;29:281e94.
61. Chang MC, Nevadunsky NS, Viswanathan AN, et al. Endocervical adenocarcinoma
in situ with ovarian metastases: a unique variant with potential for long term survival.
Int J Gynecol Pathol 2010;29:88e92.
62. O’Neill CJ, McCluggage WG. p16 expression in the female genital tract and its
value in diagnosis. Adv Anat Pathol 2006;13:8e15.
63. Vang R, Gown AM, Farinola M, et al. p16 expression in primary ovarian mucinous
and endometrioid tumors and metastatic adenocarcinomas in the ovary: utility for
identification of metastatic HPV-related endocervical adenocarcinomas. Am J Surg
Pathol 2007;31:653e63.
64. Wentzensen N, Du Bois A, Kommoss S, et al. No metastatic cervical
adenocarcinomas in a series of p16INK4A positive mucinous or endometrioid
advanced ovarian carcinomas: an analysis of the AGO Ovarian Cancer Study Group.
Int J Gynecol Pathol 2007;27:18e23.
65. Houghton O, Jamison J, Wilson R, et al. p16 immunoreactivity in unusual types of
cervical adenocarcinoma does not reflect human papillomavirus infection.
Histopathology 2010;57:342e50.
66. Rodriguez IM, Irving JA, Prat J. Endocervical-like mucinous borderline tumors of the
ovary: a clinicopathologic analysis of 31 cases. Am J Surg Pathol 2004;28:1311e18.
67. Vang R, Gown AM, Barry TS, et al. Immunohistochemistry for estrogen and
progesterone receptors in the distinction of primary and metastatic mucinous tumors
in the ovary: an analysis of 124 cases. Mod Pathol 2006;19:97e105.
68. Vang R, Gown AM, Barry TS, et al. Ovarian atypical proliferative (borderline)
mucinous tumors: gastrointestinal and seromucinous (endocervical-like) types are
immunophenotypically distinctive. Int J Gynecol Pathol 2006;25:83e9.
69. Yasunaga M, Ohishi Y, Oda Y, et al. Immunohistochemical characterization of
mullerian mucinous borderline tumors: possible histogenetic link with serous
borderline tumors and low-grade endometrioid tumors. Hum Pathol
2009;40:965e74.
J Clin Pathol 2012;65:596e600. doi:10.1136/jcp.2010.085688