MIB-1 in Endometrial Carcinoma: Prognostic Significance with 5-Year Follow-Up

Geisler, John P.; Geisler, Hans; Miller, Greg A.; Wiemann, Michael C.; Zhou, Zijie; Crabtree, William N.

doi:10.1006/gyno.1999.5615

Cited by 42 publications

(42 citation statements)

References 35 publications

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“…Among proliferation markers, Ki-67 has been suggested to provide additional information regarding clinical course and prognosis. 17,29,30 In agreement with previous series, we observed reactivity for Ki-67 in half of our cases, which increased as age, FIGO grade and stage, and myometrial invasion progressed, 28 and as a trend with nonendometrioid type and presence of lymph-vascular invasion. 29 These findings point to a severe deregulation of the cell cycle in cases with more aggressive behaviour and, in fact, our patients had shorter survival.…”

Section: Discussionsupporting

confidence: 92%

“…29 These findings point to a severe deregulation of the cell cycle in cases with more aggressive behaviour and, in fact, our patients had shorter survival. 29,30 However, data on the prognostic relevance of Ki-67 in endometrial carcinoma are variable. 28 Finally, although our HER-2/neu positive tumours (immunohistochemistry or CISH/FISH) contained frequently high levels of Ki-67 and accumulated p53, which would agree with their role in cell proliferation, 17 the results did not reach significant correlation.…”

Section: Discussionmentioning

confidence: 99%

“…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. [28][29][30] We, therefore, studied the amplification status of the HER-2/neu gene by CISH from 60 archival specimens of endometrial carcinoma. The results were compared with the corresponding HER-2/neu (A0485 and TAB250), p53, and Ki-67 protein expression determined by immunohistochemistry, several clinicopathologic factors, and the outcome.…”

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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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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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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“…The most frequently used antibody of this kind is MIB-1, which was first reported by Cattoretti et al in 1992. 25 The proliferative activity determined by MIB-1 has generally confirmed the findings obtained with the original Ki-67 antibody; that is, correlation with tumour grade, [30][31][32] clinical course, [33][34][35][36] and other methods for the evaluation of growth rate. 30 31 37 "A major drawback of the prototypic Ki-67 antibody is that it can be used on frozen sections only" It is expected that the application of the various Ki-67 equivalent antibodies should produce similar staining results, although to our knowledge comparisons of the qualitative and quantitative staining properties of Ki-67 equivalent antibodies under standardised conditions have not been reported previously.…”

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confidence: 54%

Comparison of Ki-67 equivalent antibodies

Lindboe¹,

Torp²

2002

Journal of Clinical Pathology

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Aims: To compare commercially available Ki-67 equivalent antibodies with regard to qualitative and quantitative immunohistochemical staining characteristics. Methods: The following antibodies were used: monoclonal MIB-1 (Immunotech), monoclonal MM1 (Novocastra), polyclonal NCL-Ki-67p (Novocastra), and polyclonal Rah Ki-67 (Dako). All immunostainings were evaluated in squamous epithelium from formalin fixed and paraffin wax embedded pharyngeal tonsils. Labelling indices (LIs) were recorded twice to test their reproducibility. Results: By application of all four antibodies the nuclear staining could be either diffuse, granular, or a combination of both (classified as granular in this study). The diffuse pattern generally showed a strong or moderate staining intensity, whereas the granular pattern displayed a continuum from strong to very weak, making it difficult to discriminate between positive and negative nuclei. The diffuse staining pattern was seen in approximately 59% of the nuclei with the MIB-1 antibody and in 35-45% when the other antibodies were used. The following mean LIs were recorded: MIB-1, 31%; NCL-Ki-67p, 21%; Rah Ki-67, 17%; and MM1, 14%. The reproducibility was excellent for all four antibodies, with the mean of differences between the two runs of counts ranging from 1.1% to 1.5%. Conclusions: The four tested Ki-67 equivalent antibodies revealed differences in qualitative and quantitative staining characteristics, which resulted in considerable variations in registered LIs. The MIB-1 antibody appears to have a higher sensitivity for detecting the Ki-67 antigen than the other three tested antibodies. These differences are important to consider when proliferative activity is determined by the Ki-67 LI.

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“…49 Some studies have shown that a combination of markers including p53, p16, PTEN and PR may be superior to p53 alone in discriminating uterine serous versus endometrioid carcinoma. 1,50 High proliferation index by MIB-1 stain has been shown to be of prognostic significance in endometrial carcinomas in some studies, [51][52][53] whereas others have shown no prognostic significance of MIB-1 in high-grade carcinomas of the endometrium. 54 We use MIB-1 in endometrial cancers that show complete absence of staining for p53 (p53 null), a pattern that has been shown to correlate with the presence of frameshift or nonsense p53 mutations.…”

Section: Pfs -Morphologymentioning

confidence: 99%

p53 overexpression in morphologically ambiguous endometrial carcinomas correlates with adverse clinical outcomes

et al. 2010

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The distinction between uterine serous and endometrioid carcinomas can usually be achieved by morphologic examination alone. However, there are occasional 'morphologically ambiguous endometrial carcinomas' that show overlapping serous and endometrioid features and defy histologic classification. The primary aim of this study was to assess the clinical significance of p53 overexpression using immunohistochemistry in such tumors. Related aims included (1) assessing interobserver diagnostic concordance for histologic subclassification of these tumors using a panel of pathologists with and without gynecologic pathology expertise and (2) elucidating the histologic features that correlate with p53 status. Thirty-five such cases were identified during the study period. p53 overexpression was seen in 17 of 35 cases. Tumors with p53 overexpression were associated with a significantly inferior progression-free survival and disease-specific survival compared with those that lacked p53 overexpression (3-year progression-free survival and disease-specific survival were 94 and 100% in patients with no p53 overexpression, and 52 and 54% in patients with p53 overexpression; P ¼ 0.02 and 0.003, respectively). The consensus diagnosis rendered by gynecologic pathologists was predictive of disease-specific survival (P ¼ 0.002), but not progression-free survival (P ¼ 0.11). Although the interobserver diagnostic concordance (kappa ¼ 0.70) was substantial for gynecologic pathologists, and highly associated with p53 status (77% of 'favor serous' cases showed p53 overexpression, whereas only 25% of 'favor endometrioid' cases showed p53 overexpression; P ¼ 0.005), the concordance between the consensus diagnosis of the two specialized pathologists versus each of three non-specialized pathologists was poor (kappa ¼ 0.13-0.25). The histologic feature that correlated most with p53 overexpression was the presence of diffuse high nuclear grade. p53 immunohistochemistry assays in morphologically ambiguous endometrial carcinomas are roughly as clinically informative as gynecologic pathology consultation and can be helpful for prognostic assessment and therapeutic decision making in difficult endometrial carcinomas.

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MIB-1 in Endometrial Carcinoma: Prognostic Significance with 5-Year Follow-Up

Cited by 42 publications

References 35 publications

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

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

Comparison of Ki-67 equivalent antibodies

p53 overexpression in morphologically ambiguous endometrial carcinomas correlates with adverse clinical outcomes

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