Absence of overexpression of p53 protein by intestinal carcinoid tumours

O'Dowd, Gerry; Gosney, John R.

doi:10.1002/path.1711750407

Cited by 31 publications

(11 citation statements)

References 9 publications

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“…A few studies have reported p53 protein overexpression or p53 gene mutation in intestinal carcinoid tumors [39, 40, 41]. Along with our results, p53 overexpression has been reported to be absent in carcinoid tumors smaller than 20 mm or with submucosal invasion [40, 41].…”

Section: Discussionsupporting

confidence: 75%

Growth Characteristics of Rectal Carcinoid Tumors

et al. 2000

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Purpose: Tissue growth depends on both cell proliferation and cell death. This study was designed to examine the growth characteristics of rectal carcinoid tumors. Methods: Fifty rectal carcinoid tumors were studied clinicopathologically and experimentally. Expression of Ki-67, TGF-α, p53, and bcl-2 was examined immunohistochemically, and apoptotic cells were identified by the in situ DNA nick end labeling method. EGF receptor expression was examined by a colorimetric in situ mRNA hybridization technique. Results: The median Ki-67 labeling index (LI) in all lesions was 0.62 ± 0.59%. Ki-67 LI was significantly (p < 0.01) higher in lesions larger than 5 mm than in lesions smaller than 5 mm. TGF-α was expressed more frequently (p < 0.01) in lesions larger than 5 mm (100%) than in lesions smaller than 5 mm (65.2%). Ki-67 LI was significantly (p < 0.05) higher in lesions with TGF-α expression than in lesions without TGF-α expression. The in situ hybridization revealed EGF receptor expression in all 46 lesions with intact mRNA (100%), and coexpression of TGF-α and EGF receptor was found in 39 of the 46 (84.8%) lesions. The median apoptotic index (AI) in all lesions was 0.15 ± 0.12%. AI has increased with tumor size and was significantly (p < 0.05) higher in lesions with a higher Ki-67 LI than in lesions with a lower Ki-67 LI. p53 protein was detected in only 1 patient who had liver metastases, and the gene mutation was confirmed by polymerase chain reaction and single-strand conformation polymorphism analysis. bcl-2 expression was absent in all lesions. Conclusions: The Ki-67 LI indicated a low cellular proliferative activity in rectal carcinoid tumors. AI was very low, and was significantly correlated with proliferative rate. Inhibition of apoptosis by mutated p53 or bcl-2 may not have occurred in most of these tumors. TGF-α/EGF receptor autocrine mechanisms may play a possible role in tumor growth, and the cellular proliferative activity may increase as tumors grow larger.

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Section: Discussionsupporting

confidence: 75%

Growth Characteristics of Rectal Carcinoid Tumors

et al. 2000

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“…This is corroborated by lack of allelic loss of 17p, the chromosomal location of the p53 gene in tumors associated with pseudomyxoma peritonei in a previous study (17). Similarly, appendiceal carcinoid tumors have infrequent p53 gene mutations (19,20).…”

Section: Discussionsupporting

confidence: 62%

Mucinous and Nonmucinous Appendiceal Adenocarcinomas: Different Clinicopathological Features but Similar Genetic Alterations

et al. 2002

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The genetic alterations of appendiceal carcinomas have not been reported in detail. We studied the clinicopathological factors and genetic alterations including microsatellite instability, p53 overexpression, and mutations of the K-ras proto-oncogene of 30 appendiceal adenocarcinomas, consisting of 23 mucinous and 7 nonmucinous carcinomas. Sixteen (70%) mucinous carcinomas presented with pseudomyxoma peritonei, but 6 of 7 (86%) nonmucinous carcinomas presented with appendicitis (P ‫؍‬ .002). All carcinomas were microsatellite stable, and p53 overexpression was present in only 1 of 30 (3%) carcinomas. K-ras mutation was present in 11 of 20 (55%) carcinomas, including 8 of 16 (50%) mucinous and 3 of 4 (75%) nonmucinous carcinomas. The mean survival of patients with mucinous carcinomas was 26 ؎ 19 months compared with 13 ؎ 9 months for patients with nonmucinous carcinomas (P ‫؍‬ .0002). Our findings suggest that mucinous and nonmucinous carcinomas of appendix have similar genetic alterations, but different clinical presentation and prognosis. KEY WORDS: Adenocarcinoma, Appendix, K-ras, Microsatellite instability, p53. Mod Pathol 2002;15(6):599 -605Appendiceal carcinoma is an uncommon malignancy of the gastrointestinal tract with a prevalence ranging from 0.2 to 0.3% of appendectomy specimens (1, 2). Most appendiceal carcinomas arise from an adenomatous polyp or serrated adenoma (3-5) and present clinically with pseudomyxoma peritonei. Most colorectal cancers develop from adenomatous polyps, and morphological and genetic progression in an adenoma-adenocarcinoma sequence and in hereditary colorectal cancer syndromes are well described (6 -9). The majority of colorectal cancers have truncating mutations or deletions of the adenomatous polyposis coli (APC) gene on chromosome 5q or mutations of the ␤-catenin gene. Point mutations of the K-ras protooncogene and mutations and/or deletions of the p53 gene on chromosome 17p are also common. In a second pathway to colorectal neoplasia, microsatellite instability (MSI; also termed DNA replication errors and ubiquitous somatic mutations) is caused by mutations in a nucleotide mismatch repair gene, including hMSH2, hMLH1, PMS1, PMS2, and GTBP (6 -9). MSI is characterized by additions and deletions of nucleotides in numerous repeated nucleotide sequences (microsatellites). MSI is frequent in the right-sided colon carcinomas and mucinous colorectal carcinomas (6 -9).The genetic alterations in appendiceal carcinoma have not been reported in detail. We therefore studied MSI, p53 overexpression, and K-ras mutations in appendiceal carcinomas and compared these genetic alterations with the clinicopathologic findings. MATERIALS AND METHODS Case MaterialA computer search of MD Anderson Cancer Center surgical pathology diagnoses from 1995 through 2000 was performed. Primary appendiceal carcinomas were identified using the World Health Organization classification of appendiceal carcinomas (10). There were 30 patients with primary appendiceal carcinomas and available paraffin-embedded bloc...

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“…Vortmeyer et al (25) found loss of heterozygosity of p53 in PDEC and colorectal adenocarcinoma but not in WDET. Other authors described the absence of p53 overexpression in WDETs (26,27). Because the immunohistochemical expression of p53 in colorectal tumor tissues is inconsistent, we preferred to evaluate the p53 mutational status by single-strand conformation polymorphism-PCR as described before (7).…”

Section: Discussionmentioning

confidence: 99%

Loss of Nuclear p27 Expression and Its Prognostic Role in Relation to Cyclin E and p53 Mutation in Gastroenteropancreatic Neuroendocrine Tumors

Grabowski¹,

Schrader

Wagner

et al. 2008

Clinical Cancer Research

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Purpose: Gastroenteropancreatic neuroendocrine tumors (GEP-NET) are classified by the WHO, yet its prognostic value needs to be confirmed. Therefore, we aimed to determine the prognostic role of cell cycle key regulatory genes p53, p27 kip1 (p27), and cyclin E in this tumor entity. Experimental Design: Tumor specimen from 89 patients with a complete follow-up were studied immunohistochemically for p27 and cyclin E expression and for p53 mutations. The functional relevance of p27 was evaluated in the neuroendocrine cell lines BON1 (human) and INS1 (rat) by the use of small interfering RNA. Results: Twenty-six of 29 benign, well-differentiated endocrine tumors (WHO class 1) showed a high expression (>50%) of p27, whereas all 10 poorly differentiated endocrine carcinomas (WHO class 3) displayed a low expression of p27. Metastatic well-differentiated endocrine carcinomas (WHO class 2) showed a low p27 expression in 20 of 50 (40%) patients, which conferred a poor prognosis (median survival, 57 versus 140 months; P = 0.037). This prognostic dichotomy was improved by the use of a combination of p27 and cyclin E (high cyclin E/low p27 versus low cyclin E/high p27: median survival 53 months versus not reached; P = 0.0044). p53 mutations were rare (1of 10 poorly differentiated endocrine carcinomas). Conclusions: Loss of p27 and overexpression of cyclin E play a critical role in the aggressiveness of gastroenteropancreatic neuroendocrine tumors. This coincides with increased cell cycle progression. We propose a discussion whether to incorporate the immunohistochemical expression of p27 into a revised classification to individualize therapeutic strategies in this tumor entity.

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Absence of overexpression of p53 protein by intestinal carcinoid tumours

Cited by 31 publications

References 9 publications

Growth Characteristics of Rectal Carcinoid Tumors

Growth Characteristics of Rectal Carcinoid Tumors

Mucinous and Nonmucinous Appendiceal Adenocarcinomas: Different Clinicopathological Features but Similar Genetic Alterations

Loss of Nuclear p27 Expression and Its Prognostic Role in Relation to Cyclin E and p53 Mutation in Gastroenteropancreatic Neuroendocrine Tumors

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