Small Advanced Colorectal Cancers: Clinicopathological Characteristics and Pathogenetic Origin

Abstract

Background:Recently, increasing numbers of small but deeply invading colorectal cancers have been detected. We conducted the present study to examine the hypothesis that these small advanced cancers are more biologically malignant than larger cancers and to elucidate their pathogenetic origin. Methods: We analyzed the clinicopathological characteristics of 23 advanced cancers not exceeding 2 cm in diameter (Small-Ca) in comparison with 1117 advanced cancers larger than 2 cm (Large-Ca). We compared the frequency of K-ras mutation and the growth pattern (polypoid growth, PG; non-polypoid growth, NPG) between Small-Ca and 60 submucosal cancers not exceeding 2 cm in diameter (Early-Ca). Results: Generally, Small-Ca showed less malignant characteristics than Large-Ca. However, Small-Ca with NPG pattern invaded more deeply and metastasized more frequently than those with PG pattern. In Small-Ca, all ulcerated lesions showed NPG pattern, whereas only 14% of protruded lesions did. In Early-Ca, 90% of non-polypoid lesions showed NPG pattern, whereas only 16% of polypoid lesions did. K-ras mutation was less frequent in ulcerated Small-Ca than in polypoid cancers (33 vs 57%). In Early-Ca, non-polypoid cancers showed a lower frequency of K-ras mutation than polypoid cancers (9% vs 46%). Conclusions: Small-Ca, in general, were less malignant clinicopathologically than Large-Ca; however, Small-Ca with NPG pattern showed a tendency to be more aggressive than those with PG pattern. The similarity of the K-ras mutation rate and growth pattern of ulcerated SmallCa and non-polypoid Early-Ca suggests that the majority of ulcerated Small-Ca may originate from non-polypoid Early-Ca.

Small, flat colorectal cancers in the UK population: an analysis of resected specimens

“…The 1% incidence of diminutive (£10 mm), flat or depressed colorectal cancer seen in resected colon approached that of colonoscopic studies [28]. Ishihara et al analysed small, flat resected colorectal cancers (£20 mm), and demonstrated an overall incidence of 1.3% with 15 of 23 (65%) of small cancers having flat or depressed morphology [29] ( Table 2).…”

“…Detection rates at colonoscopy are shown in Table 1 [12,16,17,[20][21][22][23][24][25][26][27]. There are no large papers from Western countries which have studied the prevalence of flat cancers in resected specimens (see Table 2 [28][29][30]). Kubota et al [28] and Stolte and Bethke [19] prospectively assessed resected colon for the background incidence of diminutive flat adenocarcinomas, defined as lesions with a maximum diameter of 10 mm.…”

“…Kubota et al [28] and Stolte and Bethke [19] prospectively assessed resected colon for the background incidence of diminutive flat adenocarcinomas, defined as lesions with a maximum diameter of 10 mm. Ishihara et al [29] and Nasir et al [30] retrospectively compared a number of polypoid and nonpolypoid tumours of all sizes. In both papers there were difficulties in classifying tumours with mixed growth patterns or surface ulceration, leading to a number of exclusions.…”

“…Detection rates at colonoscopy are shown in Table 1 [12,16,17,20–27]. There are no large papers from Western countries which have studied the prevalence of flat cancers in resected specimens (see Table 2 [28–30]). Kubota et al.…”

“…Ishihara et al. [29] and Nasir et al. [30] retrospectively compared a number of polypoid and nonpolypoid tumours of all sizes.…”