Clinical and biologic heterogeneity of hereditary nonpolyposis colorectal cancer

Piero Benatti, Luca Roncucci, Dorval Ganazzi, Antonio Percesepe, Carmela Di Gregorio, Monica Pedroni, Francesca Borghi, Elisa Sala, Alessandra Scarselli, Mirco Menigatti, Giuseppina Rossi, Maurizio Genuardi, Alessandra Viel, Maurizio Ponz De Leon

Research output: Contribution to journalArticlepeer-review


MMR gene mutations and MSI are not found in all clinically diagnosed HNPCC families. We evaluated whether MMR genotyping and tumor MSI analysis could identify distinct clinical subgroups among HNPCC families. Twenty-nine clinical HNPCC families were divided into 3 groups: A, families with hMLH1 or hMSH2 gene mutations; B, MMR gene mutations not present but MSI present in at least 50% of tumors tested; C, mutational and MSI analyses negative. We evaluated tumor spectrum, age at onset, risk of cancer in the follow-up and survival for CRC in the 3 groups. Tumors of the target organs in HNPCC (colon and rectum, endometrium, ovary, small bowel, stomach, renal pelvis and ureter) were more frequent in the first 2 groups than in the latter. Colon cancer was more frequently located in the proximal colon and showed an earlier age at onset in families with MMR gene mutation or with MSI than in families with stable tumors. Comparing the occurrence of tumors in the follow-up, in the first 2 groups patients younger than 50 years had a higher RR, which was particularly marked for CRC (RR = 18.6 for group A vs. group C, RR = 16.7 for group B vs. group C). CRC patients in the first 2 groups had a better clinical prognosis. The results of molecular analysis could distinguish, within clinically defined HNPCC families, different subgroups to which specific programs of surveillance could be addressed.

Original languageEnglish
Pages (from-to)323-328
Number of pages6
JournalInternational Journal of Cancer
Issue number5
Publication statusPublished - Sep 20 2001


  • Diagnosis
  • Follow-up
  • Hereditary nonpolyposis colorectal cancer
  • Microsatellite instability
  • Mismatch repair genes
  • Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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