ras and c-myc Protein Expression in Colorectal Carcinoma Study of Cancer-Prone Patients Felice Miller, M.D.,* Tomas M. Heimann, M.D.,) Astrid Quish, M.D.,* Daniel J. Pyo, M.D.,} Arnold Szporn, M.D.,* Giorgio Martinelli, Ph.D.,-~ Thomas M. Fasy, M.D., Ph.D.* From the Departments of } Surgery and *Pathology, Mount Sinai School of Medicine, City University of New York, New York, New York This study was performed to determine the correlation of tumor ras and c-myc oncogene expression with clinical and prognostic variables in patients prone to develop colorectal cancer. One hundred eighteen patients with colorectal cancer were studied; mean age was 40 years. Fifty-three were young patients (age 40 or less), 49 had ulcerative colitis, and 16 had multiple polyposis coli. Immunoperoxidase stains of paraffin-embedded cancer sections were performed for the c-myc and ras proteins. ras staining was found to correlate with Dukes stage and prognosis. Patients with tumors negative for ras protein stain had an actuarial five-year survival of 61 percent versus 44 percent for those tumors with a positive stain (P < 0.05). This correlation was not seen with the c-myc stain. Positive ras oncogene stain appears to be a useful indicator of advanced stage and poor prognosis in colo- rectal cancer occurring in cancer-prone patients. [Key words: Colorectal cancer; Multiple polyposis coli; Ulcer- ative colitis; Young patients; Oncogenes; ras oncogene; c-myc oncogene; Prognosis] Miller F, Heimann TM, Quish A, Pyo DJ, Szporn A, Marti- nelli G, Fasy TM. ras and c-myc protein expression in colorectal carcinoma: study of cancer-prone patients. Dis Colon Rectum 1992;35:430-435. C arcinoma of the colon and rectum is most commonly seen in older patients, with the peak incidence occurring in the seventh decade of life. When these cancers develop in young patients, they are often associated with predisposing condi- tions such as multiple polyposis coli and ulcerative colitis.L, a In patients with multiple polyposis coli, the cumulative risk of developing colorectal cancer increases with age and eventually reaches nearly 100 percent. Although patients with ulcerative co- litis have a lower incidence of colorectal cancer than do those with multiple polyposis coli, their cancer risk also increases in direct proportion to the duration of disease. 3'4 Colorectal carcinoma occasionally occurs in young patients without a Address reprint requests to Dr. Heiman.n: Department of Sur- gery, Box 1259, Mount Sinai Medical Center, One Gustave L. Le W Place, New York, New York 10029. predisposing condition, s'6 Although some young patients have a positive family history of colorectal or other cancers, the reason for early cancer devel- opment in the majority is often unclear. Several studies have demonstrated that ras and c-myc oncogene expression is frequently present in colorectal adenocarcinoma. Immunohistochem- ical stains of tissue samples from colorectal cancer occurring in the general population have shown that ras and c-myc protein products are often found in greater concentrations than in normal colonic mucosa. Some studies have also reported an asso- ciation between oncogene expression and prog- nosis. 7-~~ The expression of these oncogenes in tumors occurring in populations prone to develop colorectal cancer, however, has not been well stud- ied. The present study was undertaken to deter- mine the prognostic significance of ras and c-myc oncogene expression in colorectal cancer occur- ring in cancer-prone patients. MATERIALS AND METHODS One hundred eighteen patients with colorectal adenocarcinoma undergoing surgical treatment at Mount Sinai Hospital between 1968 and 1985 were studied retrospectively. Forty-nine patients had ul- cerative colitis, 16 had multiple polyposis coli, and 53 were young patients (age 40 or less) without a predisposing cause. Histologic slides were re- viewed by a single observer. Tumor differentiation was determined according to the classification de- scribed by Jass et al., ~ and presence of colloid lakes and signet ring cells was recorded. Tumor stage was categorized according to the Astler- Coller modification of the Dukes classification, x2 In patients with multiple tumors, histologic find- ings and the Dukes stage of the most advanced 430