Abstract

Background: The value of immunohistochemistry (IHC)-microarray analysis of pathological specimens in the management of patients is controversial, although preliminary data suggest potential benefit. We describe the characteristics of patients undergoing a commercially available IHC-microarray method in patients with peritoneal metastases (PM) and the feasibility of this technique in this population.Methods: We retrospectively analyzed consecutive patients with pathologically confirmed PM from appendiceal or colorectal primary who underwent Caris Molecular Intelligence™ testing. IHC, microarray, FISH, and mutational analysis were included and stratified by Peritoneal Carcinomatosis Index (PCI) score, histology, and treatment characteristics. Statistical analysis was performed using non-parametric tests.Results: Our study included 5 patients with appendiceal and 11 with colorectal PM. The median age of patients was 51 (IQR 39–65) years, with 11 (68%) female. The median PCI score of the patients was 17 (IQR 10–25). Hyperthermic intra-peritoneal chemoperfusion was performed in 4 (80%) patients with appendiceal primary tumors and 4 (36%) with colorectal primary. KRAS mutations were encountered in 40% of appendiceal vs. 30% colorectal tumors, while BRAF mutations were seen in 40% of colorectal PM and none of the patients with appendiceal PM (p = 0.06). IHC biomarker expression was not significantly different between the two primaries. Sufficient tumor for microarray analysis was found in 44% (n = 7) patients, which was not associated with previous use of chemotherapy (p > 0.20 for 5-FU/LV, Irinotecan and Oxaliplatin).Conclusion: In a small sample of patients with PM, the feasibility and results of IHC-microarray staining based on a commercially available test is reported. The apparent high incidence of the BRAF mutation in patients with PM may potentially offer opportunities for novel therapeutics and suggest that IHC-microarray is a method that can be used in this population.

Highlights

  • Predictive and prognostic biomarkers have been studied in different cancers with the aim of developing personalized medicine for patients [1, 2]

  • KRAS mutations were encountered in 40% of appendiceal vs. 30% colorectal tumors, while BRAF mutations were seen in 40% of colorectal peritoneal metastases (PM) and none of the patients with appendiceal PM (p = 0.06)

  • Immunohistochemistry and mutational analysis using commercially available molecular profiling testing is feasible for patients undergoing surgery for their PM, mucin content might interfere with microarray analysis

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Summary

Introduction

Predictive and prognostic biomarkers have been studied in different cancers with the aim of developing personalized medicine for patients [1, 2]. The role of immunohistochemistry (IHC)microarray analysis of pathological specimens in this paradigm is currently being investigated, and preliminary data do suggest potential utility [3, 4]. Few studies have examined the value of gene expression and molecular profiling of specimens in the setting of peritoneal metastases (PM) [5,6,7]. The role of IHC-microarray analysis of specimens from PM of appendiceal or colorectal origin is not well elucidated. There is evidence to support the association of malignant transformation and peritoneal dissemination with BRAF/KRAS mutations [11,12,13,14]. The value of immunohistochemistry (IHC)-microarray analysis of pathological specimens in the management of patients is controversial, preliminary data suggest potential benefit. We describe the characteristics of patients undergoing a commercially available IHC-microarray method in patients with peritoneal metastases (PM) and the feasibility of this technique in this population

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