P53 overexpression predicts endometrial carcinoma recurrence better than HER-2/neu overexpression

Coronado, Pluvio; Vidart, José Antonio; López-Asenjo, José A.; Fasero, María; Furió-Bacete, V.; Magrina, Javier F.; Escudero, M

doi:10.1016/s0301-2115(00)00562-5

Cited by 44 publications

(40 citation statements)

References 29 publications

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“…10,19,21,22,24,25 However, opposite results have been reported. 18,23 Nevertheless, and in line with previous data, amplified tumours were more frequent among those of nonendometrioid type, high-grade, lymph-vascular invasion present and older age.…”

Section: Discussionmentioning

confidence: 97%

“…However, identification of molecular genetic alterations that could add relevant prognostic information to the traditional factors has become one of the goals of recent research in this and other neoplasias. 25,28 The involvement of HER-2/neu gene has been suggested in several human neoplasias, and it is thought to influence the responsiveness to cytotoxic chemotherapy and prognosis. 2,8 Several methods have been proved to be useful for the assessment of HER-2/ neu status.…”

Section: Discussionmentioning

confidence: 99%

“…This wide variation may be at least in part related to inherent differences of material, as well as antibodies clones, methods of detection, and nonuniform scoring systems among the studies. 10,[18][19][20][21][22][23][24][25] HER-2/neu overexpression is thought to be the result of gene amplification. 2 FISH analysis, seen as a gold standard method for detecting gene amplification, is considered to be more accurate and quantitatively precise than immunohistochemistry.…”

Section: Discussionmentioning

confidence: 99%

“…Overexpression has been seen in 4-69% of the cases. 10,[17][18][19][20][21][22][23][24][25] Currently, molecular and clinical outcomes studies addressing gene alterations in this neoplasia are limited. 10,20,21,23 Deregulation of the mechanisms controlling cell proliferation and apoptosis is known to occur in malignant neoplasms.…”

mentioning

confidence: 99%

“…Contribution to neoplastic progression and more aggressive biologic behaviour has been suggested. 17,19,[24][25][26][27][28] Ki-67 protein is present in the nucleus of cells that are actively undergoing proliferation (not in G0 or early G1). 29 In several neoplasias, the levels of protein expression correlate well with other proliferation markers (eg mitotic count, S-phase, PCNA, cyclin A and B1), tumour growth, 17 and occasionally with prognosis.…”

mentioning

confidence: 99%

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Analysis of HER-2/neu amplification in endometrial carcinoma by chromogenic in situ hybridization. Correlation with fluorescence in situ hybridization, HER-2/neu, p53 and Ki-67 protein expression, and outcome

et al. 2004

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Fluorescence in situ hybridization (FISH) is the most widely used technique to detect HER-2/neu gene amplification; however, it is only available in some institutions. In contrast, chromogenic in situ hybridization (CISH) can be evaluated by routine light microscopy. In endometrial carcinoma there are few data concerning HER-2/neu status and prognosis. Therefore, we determined HER-2/neu gene status by CISH using a digoxigenin-labelled probe on 60 formalin-fixed paraffin-embedded endometrial carcinomas. The data were compared with the immunohistochemistry of HER-2/neu (A0485, TAB250), p53, Ki-67, clinicopathological factors, and survival. By conventional light microscopy, HER-2/neu amplification (X6 copies 450% cancer cells) was detected in 14% (8/59) tumours, HER-2/neu overexpression (410% cells moderate/strong complete membrane staining) in 22% (13/60) for A0485, and 18% (11/60) for TAB250, p53 (410% þ cells) in 61% (36/59), and Ki-67 (450% þ cells) in 50% (30/60). Discordant cases for CISH and immunohistochemistry, as well as all (2 þ ) were further analysed by FISH (Vysis). Among 10 cases (2 þ ) and not amplified by CISH, two showed lowlevel amplification by FISH. Significant correlation was found between amplification and protein overexpression (Pp0.001), and a trend with nonendometrioid type, higher grade, and older age. A better outcome (KaplanMeier) was observed for patients with nonamplified (1-5 copies per nucleus) or low-level (6-10 copies) amplification tumours, low Ki-67 expression, age o50 years, endometrioid type, low FIGO (International Federation of Obstetrics and Gynaecology) grade and stage, superficial myometrial infiltration, and no lymphvascular invasion (Pp0.036), but only as a trend for HER-2/neu protein negative (P ¼ 0.13). Cox analysis revealed age, FIGO grade and stage, myometrial infiltration, and lymph-vascular invasion to be independent prognostic factors (Pp0.05), and a trend for HER-2/neu gene copy number (0.18). In endometrial carcinoma, HER-2/neu gene status can be readily assessed by CISH in routine clinical practice, and it gives more prognostic information than HER-2/neu by immunohistochemistry. FISH analysis in (2 þ ) cases but negative by CISH may detect additional tumours with low-level amplification.

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