The pattern of cell proliferation in neoplastic and nonneoplastic lesions of ulcerative colitis

Noffsinger, Amy; Miller, Mary Ann; Cusi, Maria V.; Fenoglio‐Preiser, Cecilia M.

doi:10.1002/(sici)1097-0142(19961201)78:11<2307::aid-cncr6>3.0.co;2-j

Cited by 61 publications

(11 citation statements)

References 31 publications

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“…Long-standing inflammation presumably causes free radical-mediated DNA damage, and increases the population of actively cycling cells in the colonic crypts so that the UC mucosa may be predisposed to a mutational event. 31) Furthermore, an increase in the number of cell divisions causes telomerase shortening and may contribute to DNA aneuploidy. 32) In sporadic colorectal neoplasms, such an increase in cell divisions would be caused at least partly by K-ras mutation, which is known to upregulate the mitogenic signal transduction pathway.…”

Section: Discussionsupporting

confidence: 57%

Mutations of p53 in Morphologically Non‐neoplastic Mucosa of Long‐standing Ulcerative Colitis

Takaku

Ajioka

Watanabe

et al. 2001

Japanese Journal of Cancer Research

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Two cases of ulcerative colitis (UC)-associated carcinoma or dysplasia and morphologically non-neoplastic mucosa with p53 protein overexpression (MNNM-p53OE) were selected. DNA was extracted from the paraffin blocks of these lesions and exons 5-8 of the p53 gene were analyzed by PCR and direct sequencing. In addition, mutations in K-ras codon 12 were analyzed by PCR-RFLP methods. MNNM-p53OE was located surrounding and adjoining a coexisting carcinoma and/or dysplasia. A p53 mutation was detected in 12/22 (54.5%) MNNM-p53OE samples, 4/8 (50%) dysplasia samples and 8/8 (100%) carcinoma samples. The p53 mutations detected in MNNM-p53OE were identical to those demonstrated in the adjoining carcinoma and/or dysplasia. No K-ras codon 12 mutation was detected in any of the samples. These results indicate that MNNM-p53OE may share an identical clonal linkage with a coexisting carcinoma and/or dysplasia, and may be an initial and submorphological form of UC-associated neoplasia. Recognition of MNNM-p53OE in biopsy specimens may help to identify patients with UC at risk of developing colorectal carcinoma.

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Section: Discussionsupporting

confidence: 57%

Mutations of p53 in Morphologically Non‐neoplastic Mucosa of Long‐standing Ulcerative Colitis

Takaku

Ajioka

Watanabe

et al. 2001

Japanese Journal of Cancer Research

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“…Method Issues [200][201][202][203][204][205][206][207][208][209][210][211][212][213][214][215][216] • Immunohistochemistry (Ki-67, proliferating cell nuclear antigen) method variation • Flow cytometric method variation • Mitotic counts rarely used for carcinomas-variation in approach • Variation in number of counts performed using any method…”

Section: Proliferation Indicesmentioning

confidence: 99%

Prognostic Factors in Colorectal Cancer

Compton

Fielding

Burgart

et al. 2000

Archives of Pathology &Amp; Laboratory Medicine

928

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Background.—Under the auspices of the College of American Pathologists, the current state of knowledge regarding pathologic prognostic factors (factors linked to outcome) and predictive factors (factors predicting response to therapy) in colorectal carcinoma was evaluated. A multidisciplinary group of clinical (including the disciplines of medical oncology, surgical oncology, and radiation oncology), pathologic, and statistical experts in colorectal cancer reviewed all relevant medical literature and stratified the reported prognostic factors into categories that reflected the strength of the published evidence demonstrating their prognostic value. Accordingly, the following categories of prognostic factors were defined. Category I includes factors definitively proven to be of prognostic import based on evidence from multiple statistically robust published trials and generally used in patient management. Category IIA includes factors extensively studied biologically and/or clinically and repeatedly shown to have prognostic value for outcome and/or predictive value for therapy that is of sufficient import to be included in the pathology report but that remains to be validated in statistically robust studies. Category IIB includes factors shown to be promising in multiple studies but lacking sufficient data for inclusion in category I or IIA. Category III includes factors not yet sufficiently studied to determine their prognostic value. Category IV includes factors well studied and shown to have no prognostic significance. Materials and Methods.—The medical literature was critically reviewed, and the analysis revealed specific points of variability in approach that prevented direct comparisons among published studies and compromised the quality of the collective data. Categories of variability recognized included the following: (1) methods of analysis, (2) interpretation of findings, (3) reporting of data, and (4) statistical evaluation. Additional points of variability within these categories were defined from the collective experience of the group. Reasons for the assignment of an individual prognostic factor to category I, II, III, or IV (categories defined by the level of scientific validation) were outlined with reference to the specific types of variability associated with the supportive data. For each factor and category of variability related to that factor, detailed recommendations for improvement were made. The recommendations were based on the following aims: (1) to increase the uniformity and completeness of pathologic evaluation of tumor specimens, (2) to enhance the quality of the data needed for definitive evaluation of the prognostic value of individual prognostic factors, and (3) ultimately, to improve patient care. Results and Conclusions.—Factors that were determined to merit inclusion in category I were as follows: the local extent of tumor assessed pathologically (the pT category of the TNM staging system of the American Joint Committee on Cancer and the Union Internationale Contre le Cancer [AJCC/UICC]); regional lymph node metastasis (the pN category of the TNM staging system); blood or lymphatic vessel invasion; residual tumor following surgery with curative intent (the R classification of the AJCC/UICC staging system), especially as it relates to positive surgical margins; and preoperative elevation of carcinoembryonic antigen elevation (a factor established by laboratory medicine methods rather than anatomic pathology). Factors in category IIA included the following: tumor grade, radial margin status (for resection specimens with nonperitonealized surfaces), and residual tumor in the resection specimen following neoadjuvant therapy (the ypTNM category of the TNM staging system of the AJCC/UICC). Factors in category IIB included the following: histologic type, histologic features associated with microsatellite instability (MSI) (ie, host lymphoid response to tumor and medullary or mucinous histologic type), high degree of MSI (MSI-H), loss of heterozygosity at 18q (DCC gene allelic loss), and tumor border configuration (infiltrating vs pushing border). Factors grouped in category III included the following: DNA content, all other molecular markers except loss of heterozygosity 18q/DCC and MSI-H, perineural invasion, microvessel density, tumor cell–associated proteins or carbohydrates, peritumoral fibrosis, peritumoral inflammatory response, focal neuroendocrine differentiation, nuclear organizing regions, and proliferation indices. Category IV factors included tumor size and gross tumor configuration. This report records findings and recommendations of the consensus conference group, organized according to structural guidelines defined herein.

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“…Chronic inflammation is able to trigger increased epithelial cell proliferation, which predisposes to DNA damage, ultimately resulting in dysplasia in UC. Several analyses have shown an increase of crypt cell proliferation [9][10][11] and genetic alterations [12,13] in nondysplastic epithelium as well as in UC-associated dysplasia. Similarly, atypical mitoses, evidence of nuclear aberration, occur in areas without dysplasia as well as in dysplasia in patients with long-standing UC [14].…”

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confidence: 99%

Comparative Histologic Assessment of Proctocolectomy Specimens from Japanese and American Patients with Ulcerative Colitis with or Without Dysplasia

et al. 2005

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There have been no reports of histologic differences in ulcerative colitis (UC) between Japanese and American patients. We therefore compared histology in proctocolectomy resection specimens between Japanese patients with UC (19 cases with and 21 without dysplasia) at the Kitasato University East Hospital and American patients with UC (21 cases with and 24 without dysplasia) at the University of Washington Medical Center. In cases of UC with, but not without dysplasia, cryptitis (p = 0.010) and epithelial apoptosis (p < 0.001) in the nondysplastic mucosa were more frequently observed in Japanese than in American cases, whereas lamina propria fibrosis was more prominent in American counterparts (p = 0.008). In patients with UC with dysplasia, the duration of disease was significantly longer in American than in Japanese patients (median, 17 vs 14 years, respectively; p = 0.038). This might, in part, explain the histologic variation. Another possibility for the differences is that the preoperative medications may have differed in the populations.

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The pattern of cell proliferation in neoplastic and nonneoplastic lesions of ulcerative colitis

Cited by 61 publications

References 31 publications

Mutations of p53 in Morphologically Non‐neoplastic Mucosa of Long‐standing Ulcerative Colitis

Mutations of p53 in Morphologically Non‐neoplastic Mucosa of Long‐standing Ulcerative Colitis

Prognostic Factors in Colorectal Cancer

Comparative Histologic Assessment of Proctocolectomy Specimens from Japanese and American Patients with Ulcerative Colitis with or Without Dysplasia

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