Nup88 (karyoporin) in human malignant neoplasms and dysplasias: correlations of immunostaining of tissue sections, cytologic smears, and immunoblot analysis

Our plain-English summary of Nup88 (karyoporin) in human malignant neoplasms and dysplasias: correlations of immunostaining of tissue sections, cytologic smears, and immunoblot analysis, by V.E. Gould, A. Orucevic, H. Zentgraf, et al (Human Pathology, 2002).

The study

• Authors: V.E. Gould, A. Orucevic, H. Zentgraf, P. Gattuso, N. Martinez, A. Alonso
• Journal: Human Pathology
• Published: 2002;33(5):536-44
• Cited by: 46 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Nuclear pore complexes (NPCs) are elaborate macromolecular structures that regulate the bidirectional nucleocytoplasmic traffic system. In vertebrate cells, NPCs include a family of 50 to 100 proteins termed nucleoporins (Nups). The 88-kD Nup has been found to be linked in a dynamic subcomplex with the oncogenic CAN/Nup214. Applying a polyclonal antiserum to Nup88 on paraffin sections, we found that it immunoreacts with numerous malignant neoplasms. All carcinomas reacted irrespective of site, type, or degree of differentiation; often, high-grade carcinomas stained more strongly and extensively. Some sarcomas (e.g., fibrosarcomas, leiomyosarcomas, liposarcomas, and rhabdomyosarcomas) reacted intensely; melanomas, gliomas, mesotheliomas, and malignant lymphomas also stained. In situ carcinomas of the colon, stomach, breast, and prostate stained convincingly, as did in situ melanomas; some samples of fetal tissues also reacted. Cytologic smears of some of the aforementioned tumors also stained. In selected samples, enhanced immunostaining of tissue sections and cytologic smears correlated strongly and consistently with immunoblot data. Immunoblots of the same tumors with antibodies to 2 other Nups (Nup214 and Nup153) showed no comparable enhancement. Therefore, it seems that in some malignant tumors, Nup88 overexpression is not parallelled by an overexpression of other Nups. Benign tumors, hyperplasias, and normal tissues showed weak and sporadic staining or absence of staining; immunoblots of the same samples yielded weak signals. Occasional highly proliferative hyperplastic-reactive processes showed focal staining. Thus, our correlative histologic, cytologic, and molecular data indicate that Nup88 may be viewed as a potentially useful, broadly based histodiagnostic and molecular marker of many malignancies and premalignant dysplasias, and further suggest that in some malignant tumors, Nup88 may be selectively overexpressed as compared with other Nups. Thus, we propose that Nup88 be designated as karyoporin.

Copyright 2002, Elsevier Science (USA). All rights reserved.

In plain English

This laboratory study tested whether Nup88, a nuclear pore protein the authors proposed calling karyoporin, could be detected in tumors. The authors stained tissue from 583 cases from a Chicago hospital, mostly malignant tumors plus some dysplasias, benign tumors, and normal and fetal tissues. They compared this with cytologic smears and immunoblots, a protein test. Asbestos exposure was not examined. The authors reported that all malignant neoplasms reacted, though their table lists exceptions, such as 6 of 8 hepatocellular carcinomas. All 5 malignant mesotheliomas stained; the text calls this strong and diffuse, but the table grades it moderate to strong, with 16% to 100% of cells positive. Two benign mesotheliomas of the abdominal wall (peritoneal inclusion cysts) were negative. Benign tumors generally stained weakly and focally, though some benign bronchial carcinoids stained moderately and extensively. Two other pore proteins, Nup214 and Nup153, gave little immunoblot signal, except Nup153 in one neuroendocrine carcinoma. The authors concluded that karyoporin may evolve into a useful diagnostic marker for many cancers and some dysplasias. They noted that staining was not limited to malignant tumors and that their data were limited.

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 paraffin tissue sections and cytologic smears, compared with immunoblot analysis of selected frozen samples
• Who was studied: 583 cases from the files of Rush-Presbyterian-St Luke's Medical Center, Chicago, including 214 cases from the authors' earlier report. Samples were mostly malignant tumors, with some premalignant dysplasias, hyperplasias, reactive processes, and normal adult and fetal tissues. Dates of the cases are not given.
• Exposure: Not an exposure study. Asbestos and other exposures are not examined; the study looked at staining for the protein Nup88 with a rabbit polyclonal antiserum.
• Main results:
  • The authors stated that all malignant neoplasms immunoreacted, most with extensive staining that was at least focally strong. Their Table 1 lists some exceptions, for example 6 of 8 hepatocellular carcinomas, 18 of 19 lung neuroendocrine carcinomas, and 19 of 21 in situ melanomas.
  • Malignant mesothelioma: 5 of 5 cases stained. The authors' text describes the staining as strong and diffuse regardless of variant.
  • Table 1 grades the malignant mesothelioma staining with an extent of 3 to 5 (16% to 100% of cells positive by the table's key) and an intensity of moderate to strong.
  • Benign mesothelioma: 0 of 2 cases stained. These were benign mesotheliomas of the abdominal wall, described as multiple peritoneal inclusion cysts.
  • Benign tumors were described as showing only weak and focal staining. The authors also reported an exception: some benign bronchial carcinoids had moderate but extensive staining.
  • Nup153 on immunoblots: very scanty amounts were detected in tumors and normal tissues, except in one well-differentiated neuroendocrine carcinoma (lane 1).
  • Nup214 on immunoblots: very low signals in virtually all samples studied.
  • The authors noted that enhanced staining was not absolutely restricted to malignant tumors: focal, modest reactions were seen in some actively proliferating non-cancerous conditions.
• The authors' conclusion: The authors concluded that karyoporin (Nup88) may evolve into a potentially useful diagnostic marker for a broad spectrum of malignant neoplasms and some dysplasias, demonstrable in tissue sections and cytologic samples.
• Limitations the authors state:
  • The authors stated that their limited data do not allow a definitive answer about whether Nup88 is overexpressed separately from other nuclear pore proteins, and that further studies are needed.
  • The authors stated that the role of the overexpressed protein in malignant tumors remains speculative.

Topics

Medical terms in this study, explained in our Lexicon: Neoplasm, Carcinoma, Sarcoma, Mesothelioma.

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