Multiple primary cancer, including basal and squamous cell carcinomas of the skin with loss of mismatch-repair protein expression in a HNPCC family member – Case report

Background: Hereditary nonpolyposis colorectal cancer (HNPCC) is an inherited disease characterized by onset at an early age, an excess of synchronous and metachronous tumors and a variety of extracolorectal malignancies. Basal and squamous cell carcinomas of the skin are not customarily included in the tumor spectrum of HNPCC. HNPCC is caused by a germline mutation in one of the DNA mismatch repair (MMR) genes, most commonly MSH2 or MLH1, and typically presents with genomic instability and frequent loss of MMR protein expression in the tumor tissue.

Patient: We report the case of a 62-year old woman who had a history of colon carcinoma (cc) at the age of 46 years, endometrial cc at the age of 56 years, baso-squamous, basal, and squamous cell cc of the face at the ages of 53, 54 and 58 years, respectively, and rectal cc at 60. Her family fulfills the Amsterdam criteria. The basal, the squamous cell and the rectal carcinomas were assessed for the immunohistochemical expression of the MMR genes MLH1 and MSH2 and the p53 tumor suppressor gene.

Results: The immunohistochemical staining in both the squamous cell and the rectal cc was negative for MSH2 and positive for MLH1. The basal cell cc showed a normal immunohistochemical expression pattern for both MMR gene antibodies. All cancers were positive for the p53 gene.

Conclusion: Detection of the loss of MMR protein expression is useful to identify the gene most probably responsible for the disease and to define cancer patients who are at an increased risk of HNPCC. Testing for MMR deficiency should be performed in all patients who have a family history of colorectal cc at ≤50 years of age.

Supported by ETT No. 5K 503 and BÖ No. 5/2003.