Abstract

Rectal cancers represent 35% of colorectal cancers. Histologically, 90% of rectal cancers are adenocarcinomas, while rectal squamous cell carcinoma is very rare (0.3% of rectal cancers). Given its rarity, we have little data concerning its epidemiology, pathogenesis, prognosis and therapeutic management. The current treatment trend is to treat rectal squamous cell carcinoma by analogy with anal squamous cell carcinoma and not like rectal adenocarcinoma.

We first started by doing an exhaustive literature review aiming at giving guidance for clinician. Then we performed genomic analysis of ten rectal squamous cell carcinoma samples from Geneva and Valis. The resulting molecular profile was compared with public data for anal squamous cell carcinoma and rectal adenocarcinoma. PIK3CA, PTEN, TP53, ATM, BCL6, SOX2 are the most commonly mutated genes, a profile that is similar to squamous anal carcinoma. PIK3CA is the most commonly affected signaling pathway. HPV16 was found (by PCR amplification) in all 10 cases.

Conclusions: This report is the first comprehensive genomic characterization of rectal squamous cell carcinoma and provides evidence of genetic similarity to squamous anal carcinoma and consequently suggests the need for a similar therapeutic approach.