P53 overexpression in morphologically ambiguous endometrial carcinomas correlates with adverse clinical outcomes Journal Article


Authors: Garg, K.; Leitao, M. M.; Wynveen, C. A.; Sica, G. L.; Shia, J.; Shi, W.; Soslow, R. A.
Article Title: P53 overexpression in morphologically ambiguous endometrial carcinomas correlates with adverse clinical outcomes
Abstract: 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; P0.02 and 0.003, respectively). The consensus diagnosis rendered by gynecologic pathologists was predictive of disease-specific survival (P0.002), but not progression-free survival (P0.11). Although the interobserver diagnostic concordance (kappa0.70) 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; P0.005), the concordance between the consensus diagnosis of the two specialized pathologists versus each of three non-specialized pathologists was poor (kappa0.13-0.25). 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. © 2010 USCAP, Inc. All rights reserved.
Keywords: immunohistochemistry; adult; cancer survival; clinical article; controlled study; human tissue; aged; disease-free survival; middle aged; histopathology; cancer staging; endometrium carcinoma; endometrial neoplasms; gene overexpression; progression free survival; observer variation; tumor markers, biological; protein p53; prediction; kaplan-meiers estimate; cancer invasion; adverse outcome; tumor suppressor protein p53; outcome; cell nucleus; endometrial carcinoma; tumor classification; pathologist; p53
Journal Title: Modern Pathology
Volume: 23
Issue: 1
ISSN: 0893-3952
Publisher: Nature Research  
Date Published: 2010-01-01
Start Page: 80
End Page: 92
Language: English
DOI: 10.1038/modpathol.2009.153
PUBMED: 19855378
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 5" - "Export Date: 20 April 2011" - "CODEN: MODPE" - "Source: Scopus"
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MSK Authors
  1. Weiji Shi
    121 Shi
  2. Mario Leitao
    575 Leitao
  3. Gabriel Larkin Sica
    7 Sica
  4. Jinru Shia
    717 Shia
  5. Robert Soslow
    793 Soslow
  6. Karuna Garg
    76 Garg
  7. Christine Ann Wynveen
    11 Wynveen