The problem of de novo colorectal carcinoma

Kudo, Shin‐ei; Tamura, Shinji; Hirota, Shigeru; Sano, Yasushi; Yamano, Hiro O.; Serizawa, Masakuni; Fukuoka, Tomoki; Mitsuoka, Hiroshi; Nakajima, T.; Kusaka, Hisashi

doi:10.1016/0959-8049(95)00251-d

Cited by 115 publications

(77 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In previous studies, de novo carcinomas were characterized by rapid growth and aggressive behavior, even when under 10 mm in diameter. (3,29,30) Previously, we showed that epithelial and stromal elements demonstrate genetic instability independently in adenomas with low-or high-grade dysplasia and in advanced colorectal carcinomas, with such stromal alteration possibly influencing colorectal carcinogenesis. (10,11) In the present study, stromal MSI was found at similar low frequencies in both PG-Ca and NPG-Ca, and most of the cases, with the possible exception of D17S579 and TP53 markers, having higher stromal MSI in NPG-Ca cases.…”

Section: Discussionmentioning

confidence: 99%

Genetic instability on chromosome 17 in the epithelium of non‐polypoid colorectal carcinomas compared to polypoid lesions

Ogawa

Yoshida²,

Tsuruta³

et al. 2006

Cancer Science

View full text Add to dashboard Cite

Early colorectal carcinomas (submucosal invasive adenocarcinomas) can be classified into polypoid growth carcinoma (PG-Ca) and nonpolypoid growth carcinoma (NPG-Ca) types, the latter transforming more rapidly to advanced carcinoma. Previously, we indicated that stromal genetic instability might contribute to tumorigenesis of both sporadic and ulcerative colitis-associated colorectal adenocarcinomas. In the present study, we analyzed genetic instability of both epithelial and surrounding stromal components in PG-Ca and NPG-Ca. In 99 colorectal submucosal invasive adenocarcinomas, epithelial and stromal genetic instability was analyzed with National Cancer Institute standard microsatellite markers, chromosome 17 (Chr.17) markers and tumor suppressor gene-related markers, using a combination of the laser-captured microdissection and GeneScan approaches. Immunohistochemical analysis was carried out for hMLH1, hMSH2, MGMT and p53. In addition, we investigated methylation of the hMLH1 and MGMT promoters. The frequencies of epithelial microsatellite instability (MSI) with Chr.17 markers were significantly higher in NPG-Ca (33.3%) compared to PG-Ca (10.4%), particularly with D17S579 and D17S796. For loss of heterozygosity, only D17S786 showed a significant difference. The frequencies of stromal MSI with all markers were 31.7% and 25.9% in NPG-Ca and PG-Ca, respectively, but D17S579 and TP53 showed higher MSI in NPG-Ca than PG-Ca. Immunohistochemically, p53 protein expression in PG-Ca was significantly higher in loss of heterozygosity-positive cases with altered Chr.17 markers overall, especially the D17S796 marker, compared to cases without genetic instability. These results suggest that epithelial and stromal MSI of Chr.17 markers contributes more to carcinogenesis in NPG-Ca, whereas stromal genetic instability might be necessary for the development of both types of colorectal carcinoma. (Cancer Sci 2006; 97: 1335-1342) T wo pathways for the development of colorectal carcinoma have been proposed: the adenoma-carcinoma sequence, (1) and de novo carcinogenesis.(2) SM-Ca (invasion limited to the submucosa) have been classified histologically into two types, PG-Ca and NPG-Ca, by Shimoda et al. who suggested that the former arise from the adenoma-carcinoma sequence whereas the latter are de novo lesions that progress more easily to advanced malignancy. In colorectal carcinomas, two kinds of genetic instability are found frequently: MSI and CIN. MSI is characterized by an accumulation of somatic alterations in simple, repeated nucleotide sequences called microsatellites, (4,5) whereas CIN is characterized by LOH at sites in a number of cancer-related genes.(6,7) The precise mechanisms leading to CIN are not well understood. In sporadic colorectal carcinomas, it has been reported that approximately 15% of tumors demonstrate MSI, (8) whereas 50% exhibit LOH.Previously, we revealed not only epithelial but also stromal elements to demonstrate genetic instability in advanced colorectal carcinomas, and provided evidence that such ...

show abstract

Section: Discussionmentioning

confidence: 99%

Genetic instability on chromosome 17 in the epithelium of non‐polypoid colorectal carcinomas compared to polypoid lesions

Ogawa

Yoshida²,

Tsuruta³

et al. 2006

Cancer Science

View full text Add to dashboard Cite

show abstract

“…Non-polypoid early colorectal cancers show a flat appearance, different from polypoid-type early colorectal cancers. It still remains unclear whether these lesions derive from 'flat adenomas', supporting the concept of the adenoma-carcinoma sequence or whether they are so-called 'de novo cancers', not being preceded by adenomas (3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Small Advanced Colorectal Cancers: Clinicopathological Characteristics and Pathogenetic Origin

Ishihara¹

2000

Japanese Journal of Clinical Oncology

View full text Add to dashboard Cite

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.

show abstract

“…The "de novo" carcinogenesis: According to some reports, between 20-40% of all tumours may evolve from the colorectal mucosa de novo and grow invasively into the bowel wall [56][57][58] . Adenomatous remnants in invasive cancer have been found only in about 20% of the tumours 58,59 .…”

Section: Colorectal (Pre)neoplasiamentioning

confidence: 99%

Metachronous and Recurrent Cancer Development in Colorectal Neoplasia: Clinical Aspects, Molecular Biomarkers, and Proteomic Patterns in Surveillance and Risk Evaluation

Søreide

2008

Crit Rev Oncog

View full text Add to dashboard Cite

The problem of de novo colorectal carcinoma

Cited by 115 publications

References 5 publications

Genetic instability on chromosome 17 in the epithelium of non‐polypoid colorectal carcinomas compared to polypoid lesions

Genetic instability on chromosome 17 in the epithelium of non‐polypoid colorectal carcinomas compared to polypoid lesions

Small Advanced Colorectal Cancers: Clinicopathological Characteristics and Pathogenetic Origin

Metachronous and Recurrent Cancer Development in Colorectal Neoplasia: Clinical Aspects, Molecular Biomarkers, and Proteomic Patterns in Surveillance and Risk Evaluation

Contact Info

Product

Resources

About