Markedly elevated cell turnover is characteristic of small, deeply invasive carcinomas of the colorectum

BACKGROUND. Small, deeply invasive carcinomas invading the muscularis propr ia or deeper and measuring less than or equal to 2 cm in greatest dimension (S-ADV) are rare in comparison with their larger counterparts (NS-ADV), an d their clinicopathologic features are obscure. METHODS. S-ADV and NS-ADV cases as well as cases of submucosal carcinoma (S M-CA) were comparatively assessed for: I) clinicopathologic findings; 2) Ki -67, mitotic, and apoptotic indices; 3) cathepsin G, p53, and bcl-2 immunor eactivities; and 4) c-Ki-ms mutations. RESULTS. S-ADV and SM-CA, which both are significantly smaller than NS-ADV, did not differ in size, but the frequency of moderately and poorly differe ntiated carcinoma elements at the leading edges was observed to be higher t han in the central cores only in S-ADV, as was tumor "budding" of small clu sters of undifferentiated carcinoma cells. The frequency of severe lymphati c involvement in S-ADV was as high as in NS-ADV, and significantly greater than in SM-CA. The Ki-67, mitotic, and apoptotic indices for S-ADV were sig nificantly increased compared with those for NS-ADV and/or SM-CA. Expressio n of cathepsin G in S-ADV tumor and stromal cells was significantly decreas ed compared with NS-ADV and/or SM-CA cases. No significant differences in t he expression of either p53 or bcl-2 or the incidence of c-Ki-ras mutations were observed among the three groups. CONCLUSIONS. S-ADV can be considered a distinct type of deeply invasive car cinoma, presenting with poor tumor differentiation at the leading edge, and with increased tumor cell proliferation despite its small size. (C) 1999 A merican Cancer Society.