Worse histological grade of proximal colorectal tumors and its relation with stage.

PURPOSE: Accumulated data seem to support the concept that proximal and distal colorectal cancers (CRC) should be considered as different disease entities. We investigated a particular aspect of this assumption by examining variation of stage and grade distribution according to tumor site in a Greek patients' group. METHODS: A total of 200 cases having had undergone surgery for primary CRC was retrospectively analysed. Fifty-seven proximal tumors were compared to 143 distal lesions regarding tumor stage (TNM I-IV) and grade of differentiation (well, moderate and poor). Grade distribution by site was also examined within each particular stage and within additional stage categories (I-II, III-IV, I-III, II-IV, II-III). RESULTS: There was an almost significant trend of distal tumors for earlier stage (I) presentation (p=0.055), whereas proximal cancers were more frequently diagnosed with stages II-III (p=0.08). Poorly differentiated lesions displayed a strong predilection for proximal site (p=0.002), while tumors with moderate differentiation were preferentially found distally (p=0.001). Such segmental differences in grade distribution were also ascertained within most particular stages and all additional stage subsets (especially the last three). Moreover, both the proximal and the poorly differentiated lesions showed a parallel decrease in their incidence during the study period. CONCLUSION: The consistently recorded worse histological pattern of proximal tumors implies a different biological behavior of these lesions possibly due to distinct tumorigenic pathways involved in their development, whereas their tendency for late stage presentation demands further investigation before considered supportive to this concept.

Site impact on colorectal cancer biological behavior in terms of clinicopathological and molecular features.

PURPOSE: We investigated the biological behavior of proximal and distal colorectal adenocarcinomas (CRC), intending to determine specific segmental differences, possibly arising from the distinct genetic pathways involved in their development. METHODS: Thirty-six proximal and 83 distal cancers were comparatively and retrospectively analyzed, regarding tumor stage, grade and Ki-67, p53 and Bcl-2 immunohistochemical expression. RESULTS: Proximal tumors were more likely to be poorly differentiated (p=0.005) and to exhibit low Ki-67 and p53 expression (<20% and ≤ 30% stained nuclei respectively; p=0.026 and 0.0014, respectively). Distal lesions were more likely to be moderately differentiated (p=0.001), to display moderate Ki-67 expression (20-50% stained nuclei, p= 0.013) and p53 staining higher than 30% stained nuclei (p= 0.0014). Such segmental variations regarding mainly p53 and to a lesser extent Ki-67 were seen within most of the specific sub-groups of patients (stratified by stage, grade, gender and age). An association between Bcl-2 expression and distal site was also observed among females (p=0.008). CONCLUSION: Proximal and distal cancers displayed different clinicopathological and molecular patterns, reinforcing the proposal that they are genetically and biologically different entities. Potential clinical applications of these findings should be investigated.