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Annals of Oncology 13:1447-1453, 2002
© 2002 European Society for Medical Oncology

Original Paper

Prevalence and prognostic role of microsatellite instability in patients with rectal carcinoma

M. Colombino1, A. Cossu2, A. Manca2, M. F. Dedola3, M. Giordano4, F. Scintu4, A. Curci5, A. Avallone5, G. Comella5, M. Amoruso6, A. Margari6, G. M. Bonomo6, M. Castriota7, F. Tanda2 and G. Palmieri1,+

1 Istituto di Genetica delle Popolazioni, Consiglio Nazionale delle Ricerche, Alghero, Santa Maria la Palma; 2 Istituto di Anatomia Patologica, 3 Istituto di Scienze Radiologiche, Università di Sassari, Sassari; 4 Chirurgia Generale II, Università di Cagliari, Cagliari; 5 Istituto Nazionale Tumori ‘G. Pascale’, Napoli; 6 Chirurgia Generale, Vascolare ed Oncologica, Università di Bari, Bari; 7 Ospedali Riuniti, Foggia, Italy

Received 19 November 2001; revised 25 February 2002; accepted 27 March 2002

Background:

Association between microsatellite instability (MSI) and favorable postoperative survival in patients with colorectal cancer receiving adjuvant chemotherapy has been indicated. To evaluate whether an analogous positive prognostic role of MSI could be present in rectal carcinoma (RC; most RC patients receive adjuvant radiotherapy), PCR-based microsatellite analysis of archival RCs and statistical correlation with clinico-pathological parameters were performed.

Patients and methods:

DNA from paraffin-embedded paired samples of tumors and corresponding normal tissue from 91 RC patients was analyzed for MSI using five microsatellite markers (tumors were classified as MSI+ when two or more markers were unstable).

Results:

Seventeen (19%) RC patients exhibited a MSI+ phenotype. Prevalence of instability was found in patients with earlier RC onset (28% in cases with diagnosis age <=55 years versus 15% in cases >55 years), whereas similar MSI frequencies were observed in patients with different disease stage or receiving different adjuvant therapies. While MSI was detected in seven (64%) of 11 familial patients, a remarkably lower MSI incidence was observed in sporadic cases (10/80; 12.5%). A significant association with better disease-free survival (DFS) and overall survival (OS) was found for MSI+ patients (median DFS/OS, 30/32 months) in comparison to MSI– ones (median DFS/OS, 18/21 months) (P <0.001).

Conclusions:

MSI was demonstrated to be a strong molecular prognostic marker in rectal carcinoma, independent of the administered treatment (radiotherapy, chemotherapy or both).

Key words: microsatellite instability, polymerase chain reaction, prognosis, rectal cancer


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