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Biomarker HER2

cause gastric cancer


Introduction
• Almost every cell in our bodies has a receptor for the HER2 protein.
• Many cancers, namely gastro-oesophageal adenocarcinoma, have an
overexpression of HER2 (Rubin, 2001).
• HER2 functions as an oncogene in gastric cancer.
• Genealogical augmentation of chromosome 17 regions, which may
lead to tandem 17p duplications or double-minute chromosomes, is
linked to protein overexpression.
• Cancerous cells occur in the lining of the stomach in those who
suffer from gastric cancer (Rubin, 2001)..
• The chance of acquiring gastric cancer may be affected by factors
such as age, food, and stomach condition.
• Indigestion and abdominal pain or discomfort are common early
warning signs of gastric cancer.

• References
• Rubin I, Yarden Y. The basic biology of HER2. Ann Oncol 2001;12 Suppl
1:S3-8. 10.1093/annonc/12.suppl_1.S3 [PubMed] [CrossRef] [Google Scholar]
Methods
• Immunohistochemistry • Fluorescent in situ hybridization FISH
(IHC)
• The first screening method for • The gold standard is fluorescent in situ
HER2 evaluation hybridization (FISH), although it is seldom used
• In-situ hybridization (IHC) is owing to its greater cost, longer turnaround time,
and requirement of a fluorescence microscope.
the most common, • There are a finite number of HER2 gene copies;
inexpensive, and accessible • There is no natural degradation of stained tissues.
approach for evaluating
HER2 (Wong, 2015). • Extremely neutral and precise (yano, 2006)
• Easily accomplished;
• The majority of lab OTHER METHODS ARE
procedures are now
performed by machines; SISH: Silver in situ hybridization;
• Common and well-known CISH: Chromogenic in
amongst pathologists; situ hybridization;
• The results may be seen with
any regular bright-field DDISH: Dual-color dual-hapten in
microscope; situ hybridization.
• enables side-by-side
examination of tumor cell
morphology;
• Tissue discoloration does not
fade with time. REFERENCES
Wong DD, de Boer WB, Platten MA, Jo VY, Cibas ES, Kumarasinghe MP. HER2 testing in malignant effusions of metastatic gastric
carcinoma: is it feasible? Diagn Cytopathol. 2015;43:80–85. [PubMed] [Google Scholar]
yano T, Doi T, Ohtsu A, Boku N, Hashizume K, Nakanishi M, Ochiai A. Comparison of HER2 gene amplification assessed by
fluorescence in situ hybridization and HER2 protein expression assessed by immunohistochemistry in gastric cancer. Oncol
Rep. 2006;15:65–71. [PubMed] [Google Scholar]
Results
• Assessment of HER2 status is now required for choosing individuals suitable for this therapy, since
trastuzumab was recently introduced for the treatment of patients with advanced gastric cancer.
• Immunohistochemistry remains crucial in determining HER2 status despite the increasing availability
of in situ hybridization methods due to advances in automated platforms and image processing.
• However, there are a variety of pre-analytical, analytical, and post-analytical factors that might
compromise the overall reliability of HER2 assessment by IHC [1].
• Therefore, a specialized scoring system and, more importantly, experience in its interpretation are
both necessary when dealing with stomach and food pipe cancers.

Fig 1
expression
Of gestric her 2

• yano T, Doi T, Ohtsu A, Boku N, Hashizume K, Nakanishi M, Ochiai A. Comparison of HER2 gene amplification assessed by
fluorescence in situ hybridization and HER2 protein expression assessed by immunohistochemistry in gastric cancer. Oncol
Discussion
• In terms of cancer-related mortality, gastric cancer (GC) is a major global health problem.
• Therefore, every effort made in early diagnosis, selection of suitable therapy options, and appropriate
monitoring may play a crucial role in lowering the disease-related mortalities.
• In gestric cancer, amplification of the HER2 gene and overexpression of the protein it encodes were
shown to be strongly related with poor prognosis [1].
• In addition to being prevalent in stomach and gastroesophageal cancers, several studies have
shown that HER2 is also found especially gastric and gastroesophageal cancers.
• Many studies have shown conflicting results when examining the prognostic significance of HER2
overexpression in gastric and gastroesophageal cancer.
• Therapeutic targets and prognostic biomarkers in GC may be derived from tumor molecular
categorization and characterization, suggesting a promising direction for future research [2].
• Recurrent PIK3CA and ARID1A mutations, high expression of PD-L1 and PD-L2, excessive DNA
hypermethylation, and other features of this subtype of EBV-positive malignancy make it a promising
option for diagnostic and therapeutic biomarkers [3].
• It is possible that inhibiting DNA methylation and/or suppressing immunological checkpoints might be
effective treatments for this subtype. Multiple genes, including HER2 and HER3, are often mutated in
the MSI-high subtype [2].

• References
• 1. Akiyama T, Sudo C, Ogawara H, Toyoshima K, Yamamoto T. The product of the human c-erbB-2 gene: a 185-kilodalton
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• 2. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with
amplification of the HER-2/neu oncogene. Science. 1987;235:177–182. [PubMed] [Google Scholar]
• 3. Yan M, Schwaederle M, Arguello D, Millis SZ, Gatalica Z, Kurzrock R. HER2 expression status in diverse cancers: review of results
from 37,992 patients. Cancer Metastasis Rev. 2015;34:157–164. [PMC free article] [PubMed] [Google Scholar]

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