International Journal of Gynecological Pathology

36:412–419, Lippincott Williams & Wilkins, Baltimore

Copyright r 2017 by the International Society of Gynecological Pathologists

Original Article

Uterine Carcinosarcomas: Clinical, Histopathologic

and Immunohistochemical Characteristics

Xiaowei Chen, M.D., Rebecca Arend, M.D., Diane Hamele-Bena, M.D., Ana I. Tergas, M.D., MPH,
Melanie Hawver, M.D., Guo-Xia Tong, M.D., Thomas C. Wright, M.D.,
and Jason D. Wright, M.D.

Summary: Carcinosarcomas (malignant mixed Müllerian tumors or MMMT) are rare

malignant tumors in the female genital tract composed of both malignant epithelial and
malignant mesenchymal components. They comprise <5% of all neoplasms in the
gynecologic tract and have an aggressive clinical course. The purpose of this study is to
evaluate the immunophenotype and possible histogenesis of carcinosarcomas of the uterus.
Sixty-two cases of uterine carcinosarcomas diagnosed between 1995 and 2011 were retrieved
from the gynecologic pathology files at Columbia University Medical Center. Representative
tissue blocks containing both epithelial and mesenchymal components were selected from each
case for histologic and immunohistochemical studies. Clinical data from each case were
retrieved. The epithelial component was poorly differentiated adenocarcinoma in the majority
(80.7%) of cases; in 17.7%, the carcinoma was moderately differentiated, and in only 1.6% the
carcinoma was well differentiated. 53% of the tumors had homologous stromal elements and
47% displayed heterologous stromal elements. Immunohistochemical study revealed almost
equal staining in both epithelial and mesenchymal components of carcinosarcomas for p16
and p53. PAX8 positivity was noted in 73% of epithelial components, but only 13% of
stromal components, and PAX8 stromal positivity was never seen in the absence of PAX8
epithelial positivity. Expression of p16, p53, and PAX8 in both malignant components lends
support to the monoclonal theory of uterine carcinosarcoma tumorigenesis. The roles of these
tumor markers in the diagnosis and pathogenesis of this tumor and associations between
clinical characteristics, tumor pathologic features, and prognosis are discussed. Key Words:
Carcinosarcoma (MMMT)—Uterus—Immunohistochemistry—p16—p53—PAX8.

From the Departments of Pathology and Cell Biology
(X.C., D.H.-B., T.C.W.); Obstetrics and Gynecology, Division of
Gynecology Oncology (A.I.T., J.D.W.), Columbia University
Medical Center; Department of Pathology and Laboratory
Medicine, Staten Island University Medical Center, Northwell
Health (G.-X.T.), New York; Department of Pathology, St. Peter
Hospital, Albany (M.H.), New York; and Department of
Obstetrics and Gynecology, Alabama University of Alabama
School Medicine, Birmingham, Alabama (R.A.).
The authors declare no conflicts of interest.
Address correspondence and reprint requests to Xiaowei Chen,
MD, Columbia University Medical Center, Department of
Pathology, 630 West 168th Street, VC14-215, New York, NY
10032. E-mail: xc2159@cumc.columbia.edu.
Supplemental Digital Content is available for this article. Direct
URL citations appear in the printed text and are provided in the
HTML and PDF versions of this article on the journal’s Website,
www.intjgynpathology.com.
Carcinosarcomas, otherwise referred to as malignant
mixed Mullerian tumors or MMMT, are rare highly
aggressive malignant tumors of the female genital tract.
These tumors are biphasic, containing both malignant
epithelial and mesenchymal components. The prog-
nosis of carcinosarcomas has been reported to depend
on the histologic type of the carcinomatous compo-
nents, depth of myometrial invasion, and presence of
lymphovascular and cervical involvement (1).
Although several studies have been conducted, the
histogenesis of uterine carcinosarcomas still is not
completely understood. Two major theories of
histogenesis have been proposed: the ‘‘collision’’ or
‘‘multiclonal’’ hypothesis, which proposes that the

DOI: 10.1097/PGP.0000000000000346 412

Copyright r 2017 International Society of Gynecological Pathologists.

 UTERINE CARCINOSARCOMAS
epithelial and mesenchymal components are distinct,
coexisting populations with different cell origins, and
the alternative ‘‘monoclonal’’ hypothesis, which
suggests that carcinosarcomas arise from multipotent
stem cells differentiating along epithelial and mesen-
chymal pathways. The majority of studies favor the
‘‘monoclonal’’ theory supporting a common clonal
origin of both histologic components (2–5). In the
World Health Organization tumor classification
schema, these tumors have been redesignated as
endometrial carcinosarcoma to reflect the concept
that they are primarily epithelial tumors that have
developed a mesenchymal component (6).
Although the clinical course of carcinosarcomas is
similar to that of high-grade endometrioid cancers and
serous cancer, it is important to separate carcinosarco-
mas from other high-grade endometrial adenocarcino-
mas because carcinosarcomas have a worse prognosis.
Recently, 2 markers, p16 and p53, have been used in
the diagnosis of high-grade endometrial adenocarcino-
ma. However, few studies have described the immu-
nohistochemical profile of carcinosarcomas. Meis and
Lawrence’s (7) study demonstrated overlapping im-
munohistochemical findings between carcinosarcomas
and endometrioid adenocarcinomas and concluded
that immunohistochemistry was often not reliable or
useful in distinguishing between the 2 malignant
tumors. Some studies (8) have shown that pathologic
expression of p53 and p16 in curettage material
identified high-risk endometrial carcinoma patients
with poor prognosis. Buza and Tavassoli (9) found
p16 and p53 immunoreactivity to be concordant
between the 2 components of the same carcinosarcoma
tumor in 90% and 83% of cases, respectively.
Reviewing the literature, we found very limited
information regarding PAX8 expression in carcinosar-
comas (10). The aim of this study is to examine the
possible utility of p16, p53, and PAX8 immunohisto-
chemistry in the diagnosis of carcinosarcomas and their
potential role in the histogenesis of these tumors.
MATERIALS AND METHODS
Patient Selection
The study was approved by the Columbia Uni-
versity Institutional Review Board. Sixty-two cases of
women with uterine carcinosarcomas diagnosed from
1995 to 2011 were retrieved from our pathology files.
Patient charts were reviewed to obtain clinical
information and tumor stage. The original hematox-
ylin and eosin–stained slides from each case were
reviewed by 2 pathologists (X.C. and M.H.) to
Copyright r 2017 International Society of Gynecological Pathologists.
413
confirm the diagnoses based on established criteria
of the tumor containing malignant epithelial and
malignant stromal components (Fig. 1).
A representative formalin-fixed and paraffin-
embedded block containing both malignant epithelial
and mesenchymal components was retrieved from
each case. Immunohistochemical staining for p16
(clone E6H4, prediluted; Ventana, Tucson, AZ), p53
(clone DO7, confirm, prediluted; Ventana), and
PAX8 (rabbit polyclonal, prediluted; Cell Marque,
Rockline, CA) were performed with proper positive
and negative controls on a Ventana Medical Systems
automated stainer according to the manufacturer’s
manual. Although p16 is known to stain both the
cytoplasm and nucleus, for all 3 stains, only nuclear
staining was interpreted as positive, in accordance
with other reports (8–10). Percentage of positive
staining (P) and intensity of staining (I) were
determined separately for epithelial and mesenchymal
components. Cases were scored as follows: for
percentage of tumor cells staining, P = 0 if <5% of
cells; P = 1 if 5% to 10% of cells; P = 2 if 11% to
50% of cells; and P = 3 if >51% of cells. For
immunostaining intensity, I = 0 if no staining; I = 1
if mild intensity; I = 2 if moderate intensity; I = 3 if
strong intensity. A staining index was calculated as
the product of staining area and staining intensity.
The tumors were categorized as high-expressing
(staining index >4) or low-expressing (staining index
r4), utilizing a previously published method (11).
Statistical Methods
Staining intensity and percent of the tumor cells
were used to summarize the study data. Contingency
FIG. 1. Carcinosarcoma (hematoxylin and eosin stain, 200  ):
malignant epithelial and mesenchymal components.
Int J Gynecol Pathol Vol. 36, No. 5, September 2017
414 X. CHEN ET AL.
tables and the Fisher exact test were used to test the
association of epithelial and stromal p16, p53, PAX8
expression with demographics and clinical baseline
characteristics.
Overall survival was calculated as the time from the
date of surgery to the date of death of any cause or date
that the patient was last known to be alive. Recurrence-
free survival was calculated from the date of surgery to
the date of recurrence or death, whichever came first.
Patients who died before recurrence were censored at
the time of death. The Kaplan-Meier plots (12) were
used to estimate and illustrate the probabilities of
overall survival and recurrence-free survival. In the
univariate analysis, the log-rank test (12) was used to
assess the association of overall survival and recurrence-
free survival with age at diagnosis, obesity, nulliparity,
FIGO (International Federation of Gynecology and
Obstetrics) stage at diagnosis, histologic grade, stromal
type, and depth of invasion. Those factors with P-
values r0.20 in the univariate analysis were included in
the Cox proportional hazards model for multivariable
analysis (12).
All statistical tests were 2-sided, and P-values of
0.05 or less were considered to indicate statistical
significance.
RESULTS
The ages of the 62 patients ranged from 34 to 87 yr
old (median: 67.3 yr). The majority of patients were
postmenopausal and presented with bleeding. Other
presentations included pelvic/abdominal pain or
bloating. Almost half (30) of the patients were
clinically obese and only 8 were nulliparous.
All cases were surgical resection specimens. Tumor
stages were as follows: 23 tumors were stage I (37.1%), 10
were stage II (16.1%), 19 were stage III (30.7%), and 10
were stage IV (16.1%). Of the 62 cases, the carcinomatous
component was endometrioid type in 41 cases (66%) and
nonendometrioid type in 21 cases (34%). Nonendome-
trioid cases included serous carcinoma, clear cell carcino-
ma, and mixed types of serous/clear cell carcinoma and
other type of carcinoma. The epithelial component
appeared to be poorly differentiated adenocarcinoma in
50 cases (80.7%), moderately differentiated in 11 cases
(17.7%), and well differentiated in 1 case (1.6%). The
sarcomatous component was homologous in 33 cases
(53.2%) and heterologous in 29 cases (46.8%). Of the
tumors with heterologous stromal components, most
were rhabdomyosarcomas (44.8%) and chondrosarcomas
(34.5%). In 30 cases, <50% myometrial invasion was
identified (48.4%). The remaining 32 cases showed
Int J Gynecol Pathol Vol. 36, No. 5, September 2017
Copyright r 2017 International Society of Gynecological Pathologists.
>50% myometrial invasion (51.6%); included in these
were 6 cases with full thickness myometrial invasion.
Within the 62 cases, 2 cases had no cervical evaluation
because the cervix in one of these was not identified and
another was a supracervical hysterectomy. Twenty-three
of the remaining 60 cases showed cervical involvement
(38.3%). One case was a total hysterectomy; therefore,
only 61 of 62 cases had ovary and tube evaluation, among
which 17 cases had tumor involvement (27.9%). Thirty-
two of the 62 cases had omentectomies or pelvic side wall
biopsies, among which 9 cases had tumor involvement
(28.1%). Lymphovascular space involvement was identi-
fied in the majority of the cases (80.6%). Forty-three of
the 62 cases had lymph node evaluation, among which 32
cases had negative lymph nodes (74.4%), and 11 cases
had metastatic carcinoma (25.6%). Forty-six of the 62
cases had pelvic washings, among which 35 cases were
benign (76.1%) and 11 cases contained malignant cells
(23.9%). Clinical information and pathologic data are
summarized in Tables 1 and 2, respectively.
The staining patterns and staining indexes of p16,
p53, and PAX8 in epithelial and stromal components
are shown in Table 3. p16 staining (Fig. 2) showed
almost equal high-expression in epithelial (74%) and
mesenchymal components (71%), and p53 expression
(Fig. 3) also was similar in epithelial (48%) and
stromal (44%) components. High-expression of
PAX8 (Fig. 4) was more common in the epithelial
(73%) than mesenchymal (13%) components, and
PAX8 stromal positivity was never seen in the
absence of PAX8 epithelial positivity.
There were no significant associations among the
epithelial and stromal p16, p53, and PAX8 expression
with demographics and clinical characteristics (data
not shown).
Tables 4 and 5 show the associations of demographics
and baseline clinical characteristics with overall survival
TABLE 1. Summary of Clinical Information
Demographics No. Patients % of Patients
Age (yr)
o65 24 38.71
Z65 38 61.29
Race
White 27 43.55
Nonwhite 35 56.45
Obesity
No 19 38.78
Yes 30 61.22
(Unknown) (13)
Nulliparity
No 51 86.44
Yes 8 13.56
(Unknown) (3)
 UTERINE CARCINOSARCOMAS 415

TABLE 2. Summary of Histopathology

Pathology No. Patients % of Patients
FIGO stage
i 23 37.1
ii 10 16.1
iii 19 30.7
IV 10 16.1
Epithelial component
Endometrioid type 41 66.1
Histologic grade 1 1 2.4
Histologic grade 2 11 26.8
Histologic grade 3 29 70.7
Nonendometrioid type 21 33.9
Uterine serous carcinoma 9 42.9
Clear cell carcinoma 2 9.5
Mixed (serous/clear cell) 10 47.6
Stromal component
Homologous 33 53.2
Endometrial stromal sarcoma 11 33.3 FIG. 2. Carcinosarcoma (p16 stain, 200  ): strongly positive
Leiomyosarcoma 3 9.1 cytoplasmic staining in both epithelial and mesenchymal compo-
High grade, nonspecific sarcoma 19 57.6 nents.
Heterologous 29 46.8
Rhabdosarcoma 13 44.8
Chondrosarcoma 10 34.5
Osteosarcoma 2 6.9 significant impact on overall survival and recurrence-
Rhabdosar/chondrosar 3 10.3 free survival by multivariable analysis (Table 5).
Chondrosar/liposar 1 3.5 We found no significant association between
Depth of invasion (%)
r50 30 48.4 epithelial or stromal p16, p53, or PAX8 positivity
450 32 51.6 and overall survival or recurrence-free survival by
Other involvement multivariable analysis (data not shown).
Cervix 23 38.3
Tube/ovary 18 29.5 Median overall survival for all cases was 21 mo. Plots
Omentum/pelvic wall 9 28.1 1 to 4 demonstrate relationships between patients’ ages
Lymphovascular space 50 80.7 and FIGO stages (See Supplemental digital content 1,
involvement
Lymph node metastasis 11 25.6 http://links.lww.com/IJGP/A64) with overall survival
Malignant cells in pelvic washing 11 23.9 and recurrence-free survival. Patients younger than
65 yr had greater overall survival and recurrence-free
survival, and lower FIGO stage at diagnosis was
and recurrence-free survival. The patient’s age, FIGO associated with better greater overall survival and
stage at diagnosis and depth of invasion were statisti- recurrence-free survival.
cally significantly associated with overall survival and
recurrence-free survival by univariable analysis (Table 4).
However, only age, obesity and FIGO stage showed a

TABLE 3. Expression of p53, P16, and PAX8 in Uterine

Carcinosarcomas
n (%)
Epithelial Component Stromal Component
P16 staining index
r4 16 (26) 18 (29)
44 46 (74) 44 (71)
P53 staining index
r4 32 (52) 35 (56)
44 30 (48) 27 (44)
PAX8 staining index
r4 17 (27) 54 (87)
44 45 (73) 8 (13)
Staining index: staining area (percent cells positive) score FIG. 3. Carcinosarcoma (p53 stain, 200  ): strongly positive
(P)  staining intensity score (I). nuclear staining in epithelial and mesenchymal components.

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416 X. CHEN ET AL.

Breast and Female Genital Organs, IARC press, 2003

FIG. 4. Carcinosarcoma (PAX8 stain, 200  ): a case showing strongly
positive nuclear staining in epithelial and mesenchymal components.
DISCUSSION
Uterine carcinosarcomas are aggressive tumors
containing both malignant epithelial and mesenchymal
components. In fact, they have the worst prognosis of
all tumors in the female genital tract. In most studies
of uterine carcinosarcomas, including the World
Health Organization classification (Tumors of the
Edition), uterine carcinosarcoma is defined as a
neoplasm composed of an admixture of malignant
epithelial and stromal components, and the definition
does not take into account the histologic grade of
those malignant tissue components. We used this
definition in our study, and therefore included tumors
with well and moderately differentiated carcinomatous
components. It should be noted, however, that the
most recent World Health Organization classification
(Tumors of Female Reproductive Organs, IARC,
2014 Edition) defines uterine carcinosarcomas as
biphasic tumors with high grade carcinomatous and
sarcomatous elements.
The clinical course of carcinosarcomas is similar to
that of high-grade endometrioid adenocarcinomas and
uterine serous carcinomas, but they seem to occur in
older women. In our study, median age at diagnosis was
67 yr. Although carcinosarcomas and high-grade endo-
metrial adenocarcinomas share some clinical features,
they are clearly different morphologically. The epithelial
component of most carcinosarcomas in our study was
most often high-grade emdometrioid type or serous/
clear cell type. Although we found no significant impact
of histologic grade of the carcinomatous component on

TABLE 4. Association of Demographics and Baseline Clinical Characteristics With Overall Survival and Recurrence-free
Survival in Uterine Carcinosarcomas (Univariable Analysis)
Overall Survival (mo) Recurrence-free Survival (mo)
Prob. of Overall Prob. of Recurrence-free
Factors N Median (95% CI) Survival at 5 yr ± SE P* Median (95% CI) Survival at 5 yr ± SE P*
Overall 62 20.9 (15.9, 43.2) 0.32 ± 0.07 15.9 (9.4, 22.6) 0.19 ± 0.05
Age (yr)
o 65 24 Not reached 0.57 ± 0.11 0.008 27.4 (7.9, 161.0+) 0.35 ± 0.10 0.017
Z65 38 17.4 (15.7, 24.3) 0.16 ± 0.07 15.9 (8.5, 20.9) 0.10 ± 0.05
Obesity
No 20 17.4 (5.4, 34.1) 0.24 ± 0.11 0.19 9.9 (3.6, 20.9) 0.11 ± 0.07 0.056
Yes 30 36.1 (15.7, 129.8) 0.44 ± 0.10 24.6 (10.6, 43.2) 0.31 ± 0.09
Nulliparity
No 51 20.8 (12.4, 36.1) 0.29 ± 0.07 0.34 15.6 (8.6, 22.6) 0.19 ± 0.06 0.50
Yes 8 129.8 (1.0, 129.8) 0.53 ± 0.20 16.5 (0.4, 41.6) 0.13 ± 0.12
FIGO stage at diagnosis
I/II 33 36.1 (20.4, 107.0) 0.40 ± 0.09 0.033 23.5 (15.9, 43.2) 0.28 ± 0.08 0.005
III/IV 29 13.6 (8.8, 22.6) 0.24 ± 0.09 8.6 (5.7, 11.5) 0.11 ± 0.06
Histologic grade
Well/moderately 12 24.3 (6.1, 117.9) 0.40 ± 0.16 0.71 17.9 (6.1, 24.3) 0.08 ± 0.08 0.51
differentiated
Poorly differentiated 50 20.4 (13.6, 43.2) 0.30 ± 0.07 15.7 (9.4, 27.4) 0.22 ± 0.06
Stromal type
Homologous 33 20.4 (10.8, 107.0) 0.35 ± 0.08 0.91 17.1 (8.6, 27.4) 0.26 ± 0.08 0.27
Heterologous 29 32.9 (16.3, 54.2) 0.28 ± 0.11 15.7 (6.9, 23.5) 0.10 ± 0.06
Depth of invasion (%)
o50 30 43.2 (17.2, 107.0) 0.45 ± 0.10 0.065 24.3 (10.6, 49.6) 0.29 ± 0.09 0.021
Z50 32 16.3 (11.5, 22.6) 0.20 ± 0.08 9.9 (6.9, 18.2) 0.10 ± 0.06
*On the basis of logrank test.
CI indicates confidence interval.

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 UTERINE CARCINOSARCOMAS
TABLE 5. Association of Demographics and Baseline Clinical Characteristics With Overall Survival and Recurrence-free
Survival in Uterine Carcinosarcomas (Multivariable Analysis)
Overall Survival (mo)
Factors N HR (95% CI)
Age (yr)
o65 24 1.00
Z65 38 4.67 (1.80, 12.15)
Obesity
Yes 30 1.00
No 20 2.38 (1.03, 5.46)
FIGO stage at diagnosis
I/II 33 1.00
III/IV 29 3.38 (1.22, 9.32)
Depth of invasion (%)
o50 30 1.00
Z50 32 0.83 (0.33, 2.09)
*On the basis of Wald w2 test from Cox proportional model including those factors with a P-value r0.20 in the univariate analysis (ie, age
at diagnosis, obesity, FIGO stage, and depth of invasion).
CI indicates confidence interval; HR, hazard ratio.
overall survival, other studies have shown the subtypes
and grades of the epithelial component in carcinosarco-
mas to be significant predictors of survival (1,13).
However, the prognostic relationship between histologic
subtypes of the sarcomatous component is controver-
sial. Norris et al.’s (14) and Ferguson et al.’s (15) studies
suggested that the presence of certain heterologous
sarcomatous components portend a poor prognosis, but
a large GOG study (1) in 1990 found no significant
relationship between heterologous elements and surviv-
al. In our study, we did not identify a significant
relationship between the type of stromal differentiation
and overall survival.
Although there have been many studies reporting
immunohistochemical phenotypes in endometrial
adenocarcinomas, there are limited studies regarding
carcinocarcomas. Mayall et al. (16) suggested that
concordant staining between the epithelial and
stromal components reflected a monoclonal origin.
Chiesa-Vottero et al.’s study (17) demonstrated
overexpression of p16 and p53 in high-grade endo-
metrial and serous adenocarcinomas in the uterus
and ovary; however, only Buza and Tavassoli’s
study (9) focused on p16 and p53 in carcinosarcomas.
It is widely accepted that p16 is overexpressed in
human papilloma virus–related cervical squamous and
glandular lesions due to functional inactivation of pRb
by human papilloma virus viral oncoproteins and lack
of negative feedback on the p16 promoter. Therefore,
positive p16 immunoreactivity in gynecologic tumors
has been considered to be an indication of cervical
origin. Recent immunohistochemical studies, however,
have shown that p16 overexpression may be seen
independent of human papilloma virus infection in
Copyright r 2017 International Society of Gynecological Pathologists.
417
Recurrence-free Survival (mo)
P* HR (95% CI) P*
0.002 1.00 o0.001
4.69 (2.07, 10.64)
0.042 1.00 0.003
3.19 (1.47, 6.90)
0.019 1.00 0.002
4.42 (1.76, 11.10)
0.69 1.00 0.76
0.88 (0.40, 1.96)
some subtypes of endometrial carcinomas, for example,
squamous cells carcinoma (18), serous carcinomas (19),
clear cell carcinomas (20), and high-grade endometrioid
adenocarcinoma (21). Semczuk et al.’s study (21)
suggested that p16 inactivation may play a role in the
tumorigenesis of a subset of sporadic endometrial
carcinomas, particularly in cases exhibiting aggressive
clinical behavior. Tsuda et al. (22) proposed that p16
expression may be an early event in the neoplastic
transformation of endometrial cancer. Buza and
Tavassoli (9) reported that p16 was diffusely expressed
in carcinosarcoma, indicating that it has an important
role in its tumorigenesis. The p16 staining pattern in
our study was similar to those previous reports, and
demonstrates that p16 high-expression is not only seen
in uterine serous carcinomas, but in carcinosarcomas,
as well.
It is well known that p53 plays an important role in
the tumorigeneses of many neoplasms. Engelsen et al.’s
study (8) revealed that pathologic expression of p53
and p16 was associated with poor prognosis in
endometrial carcinoma. Studies have shown that p53
mutation and LOH for TP53 occur frequently in
carcinosarcomas, and this was used for clonal study of
the 2 tumor components (23). Previous studies have
suggested that mutation of tumor suppressor gene p53
and consequent overexpression may play an important
role early on in the tumorigenesis of carcino-
sarcoma (24–27). Szukala et al. (28) demonstrated
concordant p53 staining in carcinomatous and
sarcomatous elements of carcinosarcomas in both
primary and metastatic sites and then suggested a
monoclonal origin. Similarly, we found no significant
difference in p53 staining in both malignant components
Int J Gynecol Pathol Vol. 36, No. 5, September 2017
418 X. CHEN ET AL.
of the carcinosarcomas in our study, and high
expression was noted in approximately half of our
cases, lending support to the statement that p53 seems
to play a role in the tumorigenesis of this neoplasm.
PAX8 is a member of the pair-box (PAX) family of
transcription factor genes and is critical in cell lineage
determination. Specifically, PAX8 plays an important
role in the organogenesis of thyroid, kidney, and
Müllerian tract. PAX8 is normally expressed in non-
neoplastic endometrial, endocervical, and fallopian tube
epithelium, but not in normal ovarian stroma (29). The
importance of PAX8 in the tumorigenesis of Müllerian
carcinomas is now widely accepted. As PAX8 recently
has been identified as an immunomarker for gynecologic
tumors, it has been widely investigated in ovarian
tumors (30) and endometrial cancers (31), especially
serous carcinomas; however, there are very limited studies
of its expression in carcinosarcomas. In a study by
Holmes et al. (10), all carcinosarcomas tested reportedly
expressed PAX8 in the carcinomatous component, but
not in the sarcomatous component. Our study also
showed that PAX8 was often expressed in the malignant
epithelial components, but, in addition, it also sometimes
was positive in the malignant mesenchymal components,
and PAX8 stromal positivity was only seen in the
presence of PAX8 epithelial positivity. Therefore, PAX8
may play a role in the tumorigenesis of carcinosarcomas,
and our finding of a combination of PAX8 expression in
both epithelial and stromal components lends further
support to the monoclonal theory of uterine carcinosar-
coma tumorigensis.
CONCLUSIONS
Immunohistochemical staining for p16, p53, and
PAX8 may be helpful in establishing a diagnosis of
carcinosarcoma, both primary and metastatic. Poorly
differentiated carcinomas were more likely to show
p16 stromal positivity. The patient’s age and FIGO
stage were associated with overall survival and
recurrence-free survival. We found no significant
correlations between the immunohistochemical stain-
ing patterns of these markers and survival or
recurrence-free survival. Expression of p16, p53, and
PAX8 in the both epithelial and stromal components
of these tumors lends support to the monoclonal
theory of uterine carcinosarcoma tumorigenesis.
Acknowledgment: The authors would like to thank Ms
Daniel Tsao-Wei at USC Cancer Center, Keck School of
Medicine, University of Southern California, Los Angeles
for statistical analyses.
Int J Gynecol Pathol Vol. 36, No. 5, September 2017
Copyright r 2017 International Society of Gynecological Pathologists.
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