Expression of Bcl-2 in lung neuroendocrine tumours: comparison with p53

Wang, Da-Gong; Johnston, C.F.; Sloan, James M.; Buchanan, K. D.

doi:10.1002/(sici)1096-9896(199803)184:3<247::aid-path994>3.3.co;2-g

Cited by 12 publications

(16 citation statements)

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“…Recent classification identifies four categories of NE tumors of the lung: low grade typical carcinoid (TC), intermediate grade atypical carcinoid (AC), and high grade large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC) [16]. From the molecular point of view, genetic studies has led to the suggestion that typical and atypical carcinoids are genetically distinct from high grade neuroendocrine tumors [25][26][27][28][29][30][31][32][33].…”

Section: Discussionmentioning

confidence: 65%

Molecular analysis of the HuD gene in neuroendocrine lung cancers

et al. 2010

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Section: Discussionmentioning

confidence: 65%

Molecular analysis of the HuD gene in neuroendocrine lung cancers

et al. 2010

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“…18,19,21,23,[31][32][33] In pulmonary neuroendocrine neoplasms, p53 mutations tend to occur in more aggressive histological subtypes: it is seldom seen in low-grade tumors, such as in typical carcinoid tumor, but is more frequently evident in atypical carcinoid tumor, large-cell neuroendocrine and small-cell carcinomas. [34][35][36][37][38][39][40][41][42][43][44] Our study showed infrequent p53 immunoreactivity in thymic neuroendocrine tumors; however, it was more common in intermediate-and high-grade than in low-grade thymic neuroendocrine tumors. This suggests that p53 gene mutations and overexpression could play a role in the pathogenesis of high-grade thymic neuroendocrine tumors, as has been shown in pulmonary neuroendocrine neoplasms.…”

Section: Discussionmentioning

confidence: 88%

“…With respect to histological grade in thymic neuroendocrine tumors, we found a trend in staining that was contradictory to what has been seen in the lung, namely, that lowintermediate-grade pulmonary neuroendocrine neoplasms (carcinoid and atypical carcinoid tumors) tended to express Bax, whereas high-grade pulmonary neuroendocrine neoplasms (large-cell neuroendocrine and small-cell carcinomas) tended to express Bcl-2. 16,38,40,49,50 Moreover, in the literature there are conflicting data regarding the expression of these apoptosis markers in non-neuroendocrine thymic neoplasms. [20][21][22][23][24] Thus, the relationship of a specific apoptosis marker with histological subtype of thymic neuroendocrine tumors is often variable and inconsistent, and may not be reflective of biological behavior.…”

Section: Discussionmentioning

confidence: 99%

p53, cellular proliferation, and apoptosis-related factors in thymic neuroendocrine tumors

et al. 2004

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Thymic neuroendocrine tumors are biologically aggressive neoplasms with extensive local invasion and high mortality. Although various markers of cellular proliferation and apoptosis have correlated with degrees of tumor differentiation in pulmonary neuroendocrine neoplasms, they have not been systematically studied in thymic neuroendocrine tumors. We immunostained 21 cases of thymic neuroendocrine tumors for p53, MIB-1, and the apoptosis-related markers Bcl-2, Bcl-x, and Bax. By histological classification the cases were low-grade (nine cases), intermediate-grade (eight cases), and high-grade (four cases) thymic neuroendocrine tumors. p53 was expressed in five cases: 1/9 low grade, 3/8 intermediate grade, and 2/4 high grade. The mean cellular proliferation (MIB-1) was 7.1% (range 2-12%) in low-grade thymic neuroendocrine tumors, 6.1% (range 2-15%) in intermediate-grade thymic neuroendocrine tumors, and 34.2% (range 2-80%) in high-grade thymic neuroendocrine tumors. Bcl-2 was expressed in 16 cases: 7/9 low grade, 5/8 intermediate grade, and 4/4 high grade. Bcl-x was expressed in 16 cases: 7/9 low grade, 6/8 intermediate grade, and 3/4 high grade. Bax was expressed in 13 cases: 5/9 low grade, 4/8 intermediate grade, and 4/4 high grade. The presence of mutant p53 in the tumor was associated with a statistically significant decreased mean survival (Po0.05). In contrast, either by positive or negative staining or by the score technique (staining intensity Â percentage of cells staining), the presence of Bcl-x was associated with an increased mean survival (Po0.05). Finally, a Bcl-x : Bax ratio Z1 was also associated with an increased mean survival, as compared to a Bcl-x : Bax ratio Z1 (Po0.05). Our study shows that p53 expression and certain apoptosis markers correlate with survival. The expression of these markers may account for differences in biological behavior.

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“…Previously, a high frequency of bcl-2 expression was described in different neuroendocrine tumours that do not only share their derivation from the neural crest but also grow slowly in a less aggressive manner like MTC [23]. Other than the indolent tumour growth possibly influenced by bcl-2 in those tumours, sole alterations of bcl-2 were shown to be sufficient for the development of low malignant follicular lymphomas.…”

Section: Discussionmentioning

confidence: 99%

Regulation of proliferation and apoptosis in sporadic and hereditary medullary thyroid carcinomas and their putative precursor lesions

et al. 2000

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C-cell hyperplasia (CCH) and medullary thyroid carcinoma (MTC) in patients affected by germline mutations of the RET oncogene represent an exceptional opportunity to study the regulation of proliferation and apoptosis during tumour initiation and progression. In 56 specimens [CCH, n=1; MTC with CCH, n=26; MTC, n=20; lymph-node metastasis (LNM), n=9] from 46 patients [multiple endocrine neoplasia type 2a (MEN2a), n=24; MEN2b, n=2; familiar MTC (FMTC), n=4; sporadic MTC, n-16] and 3 cases of non-neoplastic CCH, proliferation activity (MIB1), the rate of apoptosis [dUTP nick end labelling (TUNEL)] and expression of p53, bcl-2, bcl-x and bax were investigated and compared with clinical data. In MEN-associated CCH and small MTC, bcl-2 was strongly expressed, bcl-x was moderately expressed and bax was only weakly expressed. Advanced tumours and LNM did show a more heterogeneous bcl-2 staining accompanied by an increased bax expression and accelerated proliferation. The rate of apoptosis was extremely low in all investigated tumours. P53 was detectable in three patients with rapidly growing and extensively metastasising MTC. No somatic p53 mutations were found. Hereditary MTC with germline RET mutations at codon 918 (MEN2b) and codon 634 revealed a bias towards a higher proliferation activity at a younger age and are more frequently accompanied by LNM. CCH and MTC are characterised with a preponderance of bcl-2 as a factor blocking the programmed cell death. While MTC, in general, is a slowly growing tumour, a minority of tumours do progress rapidly with high proliferation. The factors leading to an accelerated tumour progression do not seem to take their effect via the regulation of apoptosis. Certain alterations of RET are supposed to have a direct or indirect implication on proliferation and, because of this, an effect on the clinical course.

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Expression of Bcl-2 in lung neuroendocrine tumours: comparison with p53

Cited by 12 publications

References 0 publications

Molecular analysis of the HuD gene in neuroendocrine lung cancers

Molecular analysis of the HuD gene in neuroendocrine lung cancers

p53, cellular proliferation, and apoptosis-related factors in thymic neuroendocrine tumors

Regulation of proliferation and apoptosis in sporadic and hereditary medullary thyroid carcinomas and their putative precursor lesions

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