Comparison of clinicopathological and genomic profiles in anal squamous cell carcinoma between Japanese and Caucasian cohorts

Abstract

Anal squamous cell carcinoma (ASCC) is a rare tumor of the gastrointestinal tract. We aimed to compare the genetic backgrounds and their effect on clinical outcomes between Japanese and Caucasian patients with ASCC. Forty-one patients diagnosed with ASCC at the National Cancer Center Hospital were enrolled and evaluated for clinicopathological features, human papillomavirus (HPV) infection, HPV genotypes, p16 expression, PD-L1, and association of p16 status with the efficacy of concurrent chemoradiotherapy (CCRT). Target sequencing for hotspot mutations in 50 cancer-related genes was performed using genomic DNA from 30 available samples. Of 41 patients, 34 were HPV-positive (among them, HPV 16 was predominant; 73.2%); 38 patients were p16-positive (92.7%); and 39 patients received CCRT, of whom 36 were p16-positive and three p16-negative. p16-positive patients showed better complete response than p16-negative patients. Among 28 samples, 15 showed mutations in PIK3CA, FBXW7, ABL1, TP53, and PTEN; no difference in mutation profiles between the Japanese and Caucasian cohorts was observed. Actionable mutations were detected in both Japanese and Caucasian patients with ASCC. Genetic backgrounds, such as the HPV 16 genotype and PIK3CA mutations, were common regardless of ethnicity. p16 status may be a prognostic biomarker for CCRT in Japanese patients with ASCC.

Figure 1

Profile of 28 Japanese patients with ASCC. All panels are aligned with vertical tracks representing 28 patients with ASCC. (a) The pattern of clinicopathological factors. (b) Evaluation of PD-L1 and p16 expression using IHC. (c) Distribution of somatic mutations detected in Japanese patients with ASCC. ASCC, Anal squamous cell carcinoma; IHC, Immunohistochemistry.

Figure 2

Profile of genomic alterations of patients with ASCC registered in GENIE. All panels are aligned with vertical tracks representing 159 individuals. (a) Patient characteristics. (b) Distribution of somatic mutations of patients with ASCC in GENIE. ASCC, Anal squamous cell carcinoma.

Figure 3

Kaplan–Meier analysis of p16 expression and progression-free survival in 38 patients receiving CCRT. Patients with p16 overexpression are indicated with a straight line and those without p16 expression with a dashed line. CCRT, Concurrent chemoradiation therapy.