Expression of the retinoblastoma-related gene Rb2/p130 is downregulated in atypical endometrial hyperplasia and adenocarcinoma

Our plain-English summary of Expression of the retinoblastoma-related gene Rb2/p130 is downregulated in atypical endometrial hyperplasia and adenocarcinoma, by T. Susini, D. Massi, M. Paglierani, et al (Human Pathology, 2001).

The study

• Authors: T. Susini, D. Massi, M. Paglierani, V. Masciullo, G. Scambia, A. Giordano, G. Amunni, G. Massi, G.L. Taddei
• Journal: Human Pathology
• Published: 2001;32(4):360-7
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The retinoblastoma-related gene Rb2/p130 encodes a protein that is a negative cell-cycle regulator normally expressed in a number of adult tissues. This protein shares many structural and functional features with the product of the retinoblastoma gene, one of the best-studied tumor-suppressor genes, and plays a fundamental role in growth control. The Rb2/p130 gene product associates with specific members of the E2F family and various cyclins, displaying a growth-suppressive activity specific for the G(0)/G(1) phases. It has been reported that Rb2/p130 is involved in the pathogenesis and progression of lung cancer and mesothelioma. We previously demonstrated for the first time that reduced immunohistochemical expression of Rb2/p130 was a strong independent predictor of poor outcome in endometrial cancer. The aim of the present study was to evaluate Rb2/p130 expression in normal, hyperplastic, and neoplastic endometrial lesions to determine whether the protein plays a significant role in endometrial carcinogenesis. We evaluated Rb2/p130 expression by immunohistochemistry staining in 102 specimens chosen to represent a spectrum of endometrial changes, including proliferative endometrium (n = 18), secretory endometrium (n = 18), simple or complex hyperplasia without atypia (n = 18), atypical hyperplasia (n = 18), and invasive carcinoma (n = 30). We found that Rb2/p130 was highly expressed in proliferative endometrium and in hyperplasia without atypia, the mean percentage of stained nuclei being 66% and 60%, respectively, but was downregulated in secretory endometrium, atypical hyperplasia, and carcinoma, with mean scores of 38%, 25%, and 22%, respectively. When categorized on a semiquantitative scale (negative v 1% to 50% v >50% positivity), endometrial cancer displayed significantly less staining than all other endometrial samples (P <.001). Poorly differentiated carcinomas (n = 9) showed a significantly lower immunoreactivity for Rb2/p130 than did well-differentiated carcinomas (n = 11; P =.005) and moderately differentiated carcinomas (n = 10; P =.03). In addition, atypical hyperplasia showed a significantly lower immunoreactivity than either proliferative endometrium (P =.003) or hyperplasia without atypia (P = 0.02). Our findings of a progressive decrease in Rb2/p130 expression from hyperplastic endometrium through atypical hyperplasia to poorly differentiated carcinomas suggest the involvement of this negative cell-cycle regulator in endometrial carcinogenesis. Furthermore, immunostaining for Rb2/p130 may prove diagnostically useful in the often difficult distinction between hyperplastic and atypical hyperplastic endometrium. HUM PATHOL 32:360-367.

Copyright 2001 by W.B. Saunders Company

In plain English

This laboratory study concerns the lining of the uterus (endometrium), not asbestos. The authors stained 102 archived tissue specimens from the University of Florence, Italy, for the Rb2/p130 protein: 18 each of proliferative endometrium, secretory endometrium, hyperplasia without atypia and atypical hyperplasia, plus 30 endometrioid adenocarcinomas. The mean percentage of stained cells was 66.6% in proliferative endometrium, 60.0% in hyperplasia without atypia, 38.0% in secretory endometrium, 24.7% in atypical hyperplasia and 21.9% in carcinoma. On a three-level scale, carcinomas showed significantly less staining than every other group. Atypical hyperplasia showed less staining than proliferative endometrium or hyperplasia without atypia. Among the carcinomas, mean staining fell from 32.3% in grade 1 tumors to 8.1% in grade 3 tumors. No link was found with tumor stage. When atypical hyperplasia and carcinoma were compared by mean percentage, they did not differ significantly. The authors concluded that the findings suggest Rb2/p130 is involved in the development of endometrial cancer. They also concluded that staining for it may help distinguish hyperplasia with atypia from hyperplasia without atypia.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory pathology study: immunohistochemical staining of archived tissue specimens
• Who was studied: 102 endometrial specimens from the files of the Department of Pathology and Oncology, University of Florence, Italy. These were 18 proliferative endometrium, 18 secretory endometrium, 18 simple or complex hyperplasia without atypia, 18 atypical hyperplasia and 30 invasive endometrioid adenocarcinomas. The carcinomas were 11 grade 1, 10 grade 2 and 9 grade 3. Dates of the specimens are not given.
• Exposure: No asbestos or other environmental exposure was studied. The study measured the amount of the Rb2/p130 protein in tissue.
• Main results:
  • Mean percentage of Rb2/p130-stained cells by group: proliferative endometrium 66.6%, secretory endometrium 38.0%, hyperplasia without atypia 60.0%, atypical hyperplasia 24.7%, carcinoma 21.9%.
  • On the semiquantitative scale, endometrial cancer showed significantly less staining than all other endometrial samples (P less than .001 per the abstract). Of the 30 carcinomas, 7 (23.3%) were negative, 23 (76.7%) were 1% to 50% positive, and none were more than 50% positive.
  • Atypical hyperplasia showed significantly lower staining than proliferative endometrium (P = .003) and hyperplasia without atypia (P = .02). 8 of the 18 atypical hyperplasias (44%) were negative.
  • Among carcinomas, mean staining was 32.3% in grade 1, 23.0% in grade 2 and 8.1% in grade 3 tumors. Grade 1 versus 3 gave P = .005; grade 2 versus 3 gave P = .03.
  • No correlation was found between Rb2/p130 expression and tumor stage or depth of myometrial invasion.
  • In secretory endometrium, all 6 negative cases were from the late secretory phase.
• The authors' conclusion: The authors concluded that the progressive decrease in Rb2/p130 from hyperplasia through atypical hyperplasia to poorly differentiated carcinoma suggests this protein is involved in endometrial carcinogenesis. They also concluded that staining for it may prove useful in distinguishing hyperplastic from atypical hyperplastic endometrium.
• Limitations the authors state:
  • The small numbers of early and intermediate secretory-phase cases do not allow conclusions about late-phase negativity.
  • When atypical hyperplasia and carcinoma were compared by mean percentage of staining rather than the semiquantitative scale, no significant difference emerged.
  • The authors called their hypothesis about how Rb2/p130 is inactivated highly speculative.

Topics

Medical terms in this study, explained in our Lexicon: Adenocarcinoma, Lung Cancer, Mesothelioma, Carcinogenesis, Immunohistochemistry, Carcinoma, Well-Differentiated.

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