<scp>ER</scp>+/<scp>PR</scp>+/<scp>TFF</scp>3+/<scp>IMP</scp>3− immunoprofile distinguishes endometrioid from serous and clear cell carcinomas of the endometrium: a study of 401 cases

Mhawech‐Fauceglia, Paulette; Li, Yan; Liu, Song; Pejović, Tanja

doi:10.1111/his.12096

Cited by 44 publications

(25 citation statements)

References 33 publications

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“…ER is a hormone‐activated nuclear transcription factor that is important in endometrial function. Whereas the reported frequency of ER positivity varies between different tumour subtypes, endometrioid carcinomas show ER expression in the great majority of cases . The current observation of frequent PAX8 and ER expression in the differentiated endometrioid component of DDECs are therefore in keeping with these prior findings.…”

Section: Discussionsupporting

confidence: 89%

Immunophenotypic features of dedifferentiated endometrial carcinoma – insights from BRG1/INI1‐deficient tumours

et al. 2016

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Aims Dedifferentiated endometrial carcinoma (DDEC) is defined by the presence of an undifferentiated carcinoma together with an endometrioid carcinoma. Inactivation of SMARCA4 (BRG1) and SMARCB1 (INI1) were recently described as potential mechanisms underlying the histologic dedifferentiation. The aim of this study is to characterize the immunophenotypic features of DDECs, particularly in cases with prototypical histologic and molecular features (BRG1/INI1-deficiency). Methods and results We evaluated PAX8, estrogen receptor (ER) and p53 immunostaining in the endometrioid and the undifferentiated components of 20 BRG1/INI1-deficient DDECs and 15 BRG1/INI1-intact DDECs, and compared the results to that of 23 grade 3 endometrioid carcinomas. The differentiated endometrioid component was positive for PAX8 and/or ER in 19 of 20 BRG1/INI1-deficient DDECs while the corresponding undifferentiated component of all 20 tumors showed a complete absence of PAX8 and ER staining. All except one of the BRG1/INI1-deficient tumors displayed a wild-type p53 staining pattern. PAX8 and ER expression in the undifferentiated component was absent in 67% and 80% of BRG1/INI1-intact DDECs respectively, while 47% of the BRG1/INI1-intact DDECs showed mutated p53 staining pattern. In comparison, absent PAX8 and ER expression were each observed in the more solid area of 48% and 48% of grade 3 endometrioid carcinomas. Conclusions The consistent absence of PAX8 and ER expression in molecularly defined (BRG1/INI1-deficient) DDECs suggest that the loss of PAX8 and ER expression is a fundamental feature of dedifferentiation. The frequent findings of mutated p53 staining pattern in BRG1/INI1-intact DDECs indicate that BRG1/INI1-intact DDECs may be biologically different from BRG1/INI1-deficient tumors.

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Section: Discussionsupporting

confidence: 89%

Immunophenotypic features of dedifferentiated endometrial carcinoma – insights from BRG1/INI1‐deficient tumours

et al. 2016

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“…Our results are consistent with those previously reported by other authors in histological studies, [12][13][14][15]19,20 where IMP3 was expressed in 90% of EC and EAIS cases, and most endometrial PSC (94%-100%) and endometrial CCC cases (57%-90%), but only a minority of EMAC (7%-25%). Nevertheless, we have noticed a trend for IMP3 to be more often expressed in EMAC with higher nuclear grade (NG 3) than those with a lower nuclear grade (NG 1 and 2).…”

Section: Discussionsupporting

confidence: 93%

“…Re-expression of IMP3 is observed in tissue sections of several human malignancies, 16 including in situ and invasive endocervical adenocarcinoma and serous and clear cell carcinoma of endometrium. [13][14][15]19,20 To our knowledge, there is little experience with the use of IMP3 in LBC cytology containing AGCs or Ac. In a small study by Lastra et al, 12 the ICC expression and utility of IMP3 and ProEx C (a monoclonal antibody cocktail shown to be positive in dysplastic squamous and endocervical lesions) were assessed in a cohort of 34 cases diagnosed as atypical glandular cells of undetermined significance (AGUS) on cytology and found that IMP3 was positive in 80% of glandular neoplasms and negative in 93% nonglandular lesions/cases negative for squamous intraepithelial lesion (SIL).…”

Section: Discussionmentioning

confidence: 99%

Expression and utility of IMP3 in the differential diagnosis of atypical glandular cells and adenocarcinoma in liquid-based cervical cytology

Ligato

Valdes

Newcomb

et al. 2016

Journal of the American Society of Cytopathology

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“…Similarly, the diagnostic utility of p16 and p53-2 markers that are highly sensitive markers for ESC given that they are expressed in up to 100% of cases-is limited by the fact that approximately one third of CCCs and grade 3 EECs show abnormal expression of these proteins. 31,41 In one recent study, the ER (+)/PR (+)/ TFF3 (+)/IGF2BP3 (À) profile significantly distinguished Am J Surg Pathol Volume 38, Number 2, February 2014 Napsin A Expression in Endometrial Clear Cell Carcinoma EEC (including grade 3 EEC) from ESC and CCC, 41 but this profile does not distinguish CCC from ESC. 31,35,37,38 However, up to 69% of high-grade EECs may display loss of expression of 1 or both receptors, 35,37 and substantial subsets of ESC and CCC may express them.…”

Section: Discussionmentioning

confidence: 99%

Frequent Expression of Napsin A in Clear Cell Carcinoma of the Endometrium

Fadare,

Desouki,

Gwin

et al. 2014

American Journal of Surgical Pathology

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The histotyping of high-grade endometrial carcinomas with clear cells may be subject to significant interobserver variability, which suggests that a biomarker that can distinguish endometrial clear cell carcinoma (CCC) from its mimics would be of diagnostic utility. This study assessed the usefulness of napsin A immunohistochemistry in the diagnosis of CCC, on the basis of an analysis of 77 cases diagnosed as such at 9 institutions. After being independently reviewed by a subset of 3 pathologists, cases for which there was diagnostic consensus among all 3 reviewers in agreement with the primary contributor (n=60) were used to establish a "consensus group" that served as a gold standard relative to which napsin A performance was assessed. Duplicate, 1.0-mm-core tissue microarrays were constructed from the 54 cases in the consensus group for which requisite materials were available, as well as from 49 endometrial endometrioid carcinomas (all grades) and 17 endometrial serous carcinomas. Napsin A immunohistochemical analysis was performed on the microarrays and on the 17 cases for which there was no diagnostic consensus, with scoring based on the proportion of immunoreactive cells (0, 1+, 2+, and 3+ indicative of 0, 1% to 25%, 26% to 49%, and ≥50% immunoreactive cells, respectively). The distribution of scores for the 49 CCC cases with evaluable cores was as follows: 0, n=6; 1+, n=6; 2+, n=8; 3+, n=29. Among the evaluable cases, the frequency of ≥1+ napsin A immunoreactivity was significantly higher in CCCs (43/49, 88%) than in endometrial serous carcinomas (1/13, 7.7%; P<0.0001) and endometrial endometrioid carcinomas (0/49, 0%; P<0.0001). The sensitivity, specificity, negative predictive value, and positive predictive value of ≥1+ napsin A expression in predicting the consensus clear cell histotype were 0.88 (95% confidence interval [CI], 0.75-0.95), 0.98 (95% CI, 0.9-1), 0.91 (95% CI, 0.86-0.96), and 0.98 (95% CI, 0.86-1), respectively. Napsin A expression was not associated with survival or clinicopathologic factors. In the group of cases without diagnostic consensus for CCC, 50% showed ≥1+ napsin A expression; all napsin A-negative cases had previously been classified as non-CCC by ≥2 reviewers, whereas only 37.5% of the napsin A-positive cases had been classified as CCC by 2 of the 3 reviewers. In conclusion, napsin A is a sensitive and specific biomarker of the clear cell histotype in endometrial carcinomas and accordingly may have diagnostic utility in their histotyping.

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ER⁺/PR⁺/TFF3⁺/IMP3⁻ immunoprofile distinguishes endometrioid from serous and clear cell carcinomas of the endometrium: a study of 401 cases

Abstract: We recommend using an ER/PR/TFF3/IMP3 immunohistochemical panel in selected cases of endometrial carcinoma where the differential diagnosis is challenging.

Cited by 44 publications

References 33 publications

Immunophenotypic features of dedifferentiated endometrial carcinoma – insights from BRG1/INI1‐deficient tumours

Immunophenotypic features of dedifferentiated endometrial carcinoma – insights from BRG1/INI1‐deficient tumours

Expression and utility of IMP3 in the differential diagnosis of atypical glandular cells and adenocarcinoma in liquid-based cervical cytology

Frequent Expression of Napsin A in Clear Cell Carcinoma of the Endometrium

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ER+/PR+/TFF3+/IMP3− immunoprofile distinguishes endometrioid from serous and clear cell carcinomas of the endometrium: a study of 401 cases

Abstract: We recommend using an ER/PR/TFF3/IMP3 immunohistochemical panel in selected cases of endometrial carcinoma where the differential diagnosis is challenging.

Cited by 44 publications

References 33 publications

Immunophenotypic features of dedifferentiated endometrial carcinoma – insights from BRG1/INI1‐deficient tumours

Immunophenotypic features of dedifferentiated endometrial carcinoma – insights from BRG1/INI1‐deficient tumours

Expression and utility of IMP3 in the differential diagnosis of atypical glandular cells and adenocarcinoma in liquid-based cervical cytology

Frequent Expression of Napsin A in Clear Cell Carcinoma of the Endometrium

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ER⁺/PR⁺/TFF3⁺/IMP3⁻ immunoprofile distinguishes endometrioid from serous and clear cell carcinomas of the endometrium: a study of 401 cases