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. 2021 May 25;11(6):944.
doi: 10.3390/diagnostics11060944.

Her2-Positive and Microsatellite Instability Status in Gastric Cancer-Clinicopathological Implications

Ana Bermúdez  1 , Isabel Arranz-Salas  2   3 , Silvia Mercado  2 , Juan A López-Villodres  2 , Virginia González  4 , Francisca Ríus  5 , María V Ortega  2   3 , Carmen Alba  2 , Isabel Hierro  3 , Diego Bermúdez  2
Affiliations

Her2-Positive and Microsatellite Instability Status in Gastric Cancer-Clinicopathological Implications

Ana Bermúdez et al. Diagnostics (Basel). .

Abstract

Gastric cancer (GC) is one of the leading causes of cancer-related death. The combination of new molecular classifications with clinicopathological data could contribute to the individualization of patients and to the development of new therapeutic strategies. We examined the various associations in two molecular types of GC: HER2-positive (human epidermal growth factor receptor 2) and microsatellite instability (MSI), assessing their influence on treatment and prognosis. A retrospective study of 142 GC patients was performed with molecular characterization through HER2 overexpression and DNA repair protein expression for MSI. The percentage of HER2-positive tumors was 13.4%, predominantly in men. Correlations were found with intestinal type, metastases, advanced stages and chemotherapy. Almost 75% of HER2-positive patients died. MSI occurred in 16.2%, associated with advanced age, female sex, distal location and intestinal type. These patients had few metastases and low stages. The percentage of deaths was higher among MSI patients who received perioperative chemotherapy. The determination of HER2 and MSI status in GC is important for their association with specific clinicopathological features and for their prognostic and predictive value.

Keywords: HER2; clinicopathological features; gastric cancer; microsatellite instability; molecular classification.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Histological types of gastric cancer according to the Lauren classification. (A,B): Intestinal type. Normal gastric mucosa and tumor nests with intestinal adenocarcinoma morphology are observed ((A), 100×; (B), 400×). (C,D): Diffuse type. There is diffuse infiltration of tumor cells, some with signet ring cell appearance ((C), 100×; (D), 400×). Hematoxylin-eosin.
Figure 2
Figure 2
HER2-positive gastric cancer (Histoscore 3+). (A,B): Immunohistochemical technique showing intense basement membrane and basolateral staining in more than 10% of the cells ((A), 100×; (B), 400×)).
Figure 3
Figure 3
Gastric cancer. Immunohistochemical staining for DNA repair proteins. Preserved immuno-expression of MLH1 ((A), 100×), MLH2 ((B), 400×), MSH6 ((C), 400×) and PMS2 ((D), 400×) proteins. (E): Loss of MLH1 expression in tumor cells (positive internal control in accompanying lymphocytes) (400×).
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