Current prognostic and predictive biomarkers for gastrointestinal tumors in clinical practice

Abstract

The pathologist emerged in the personalized medicine era as a central actor in the definition of the most adequate diagnostic and therapeutic algorithms. In the last decade, gastrointestinal oncology has seen a significantly increased clinical request for the integration of novel prognostic and predictive biomarkers in histopathological reports. This request couples with the significant contraction of invasive sampling of the disease, thus conferring to the pathologist the role of governor for both proper pathologic characterization and customized processing of the biospecimens. This overview will focus on the most commonly adopted immunohistochemical and molecular biomarkers in the routine clinical characterization of gastrointestinal neoplasms referring to the most recent published recommendations, guidelines and expert opinions.

Keywords: immunohistochemistry; molecular pathology; predictive markers; prognostic markers; targeted therapy.

Figure 1.

HER2 testing in gastroesophageal adenocarcinomas. (A) Diagnostic algorithm modified from Bartley AN, et al.(11). Tumor cell cluster is defined as a cluster of five or more tumor cells. (B) Representative immunohistochemical examples of a negative (0) case showing no reactivity in any of the tumor cells, a negative (1+) case with faint/barely perceptible membranous staining, an equivocal 2+ immunoreaction and a strongly and diffuse 3+ positive case. CISH examples of a HER2 non-amplified and an amplified case are also shown.

Figure 2.

Immunohistochemical interpretation of MMR proteins in colorectal adenocarcinoma. (A) Diagnostic algorithm for MMR staining interpretation modified from Remo, et al. (43). (B and C) Heterogeneous MMR protein expression. (B) The lesion was heterogeneous for MSH2/MSH6 status and proficient for MLH1/PMS2. The microdissected areas also showed a heterogeneous status of the MSI testing. (C) A heterogeneous MSH6 staining pattern observed in a MLH1 mutated Lynch syndrome patient. (D) A case of indeterminate positivity for MMR proteins, in which the staining intensity observed in cancer cells’ nuclei is significantly lower in comparison to surrounding stromal cells. This case was MSI at molecular testing.