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 •
(IHC) Fluorescent in situ hybridization FISH
• The first screening method for
HER2 evaluation
• In-situ hybridization (IHC) is
• The gold standard is fluorescent in situ hybridization
the most common, (FISH), although it is seldom used owing to its greater
inexpensive, and accessible
approach for evaluating cost, longer turnaround time, and requirement of a
HER2 (Wong, 2015). fluorescence microscope.
• Easily accomplished; •
• The majority of lab There are a finite number of HER2 gene copies;
procedures are now • There is no OTHER METHODS
natural degradation ARE
of stained tissues.
performed by machines;
• Common and well-known
• Extremely neutral and precise (yano, 2006)
SISH: Silver in situ hybridization;
amongst pathologists;
• The results may be seen with
any regular bright-field CISH: Chromogenic in situ hybridization;
microscope;
• enables side-by-side DDISH: Dual-color dual-hapten in
examination of tumor cell
morphology; situ hybridization.
• 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
Rep. 2006;15:65–71. [PubMed] [Google Scholar]
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
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