Reproducibility of histological cell type in high-grade endometrial carcinoma

Subclassification of endometrial carcinoma according to histological type shows variable interobserver agreement. The aim of this study was to assess specifically the interobserver agreement of histological type in high-grade endometrial carcinomas, recorded by gynecological pathologists from five academic centers across Canada. In a secondary aim, the agreement of consensus diagnosis with immunohistochemical marker combinations was assessed including six routine (TP53, CDKN2A (p16), ER, PGR, Ki67, and VIM) and six experimental immunohistochemical markers (PTEN, ARID1A, CTNNB1, IGF2BP3, HNF1B, and TFF3). The paired interobserver agreement ranged from κ 0.50 to 0.63 (median 0.58) and the intraobserver agreement from κ 0.49 to 0.67 (median 0.61). Consensus about histological type based on morphological assessment was reached in 72% of high-grade endometrial carcinomas. A seven-marker immunohistochemical panel differentiated FIGO grade 3 endometrioid from serous carcinoma with a 100% concordance rate compared with the consensus diagnosis. More practically, a three-marker panel including TP53, ER, and CDKN2A (p16) can aid in the differential diagnosis of FIGO grade 3 endometrioid from endometrial serous carcinoma. Our study demonstrates that the inter- and intraobserver reproducibility of histological type based on morphology alone are mostly moderate. Ancillary techniques such as immunohistochemical marker panels are likely needed to improve diagnostic reproducibility of histological types within high-grade endometrial carcinomas.

[1]  M. Jacobsen,et al.  Interobserver agreement for tumour type, grade of differentiation and stage in endometrial carcinomas , 1995, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[2]  C. Eng,et al.  Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. , 2000, Journal of the National Cancer Institute.

[3]  P. Clement,et al.  Endometrioid Carcinoma of the Uterine Corpus: A Review of Its Pathology With Emphasis on Recent Advances and Problematic Aspects , 2002, Advances in anatomic pathology.

[4]  H. Thaler,et al.  Serous Endometrial Cancers That Mimic Endometrioid Adenocarcinomas: A Clinicopathologic and Immunohistochemical Study of a Group of Problematic Cases , 2004, The American journal of surgical pathology.

[5]  P. Clement,et al.  Endometrioid Carcinoma of the Uterine Corpus: A Review of Its Pathology With Emphasis on Recent Advances and Problematic Aspects , 2002, Advances in anatomic pathology.

[6]  J. Sim,et al.  The kappa statistic in reliability studies: use, interpretation, and sample size requirements. , 2005, Physical therapy.

[7]  S. Kalloger,et al.  Description of a Novel System for Grading of Endometrial Carcinoma and Comparison With Existing Grading Systems , 2005, The American journal of surgical pathology.

[8]  D. Bodurka,et al.  Association of Low-Grade Endometrioid Carcinoma of the Uterus and Ovary With Undifferentiated Carcinoma: A New Type of Dedifferentiated Carcinoma? , 2006, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[9]  George L Mutter,et al.  Molecular and pathologic aspects of endometrial carcinogenesis. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  A. Tannapfel,et al.  p16, p14, p53, cyclin D1, and steroid hormone receptor expression and human papillomaviruses analysis in primary squamous cell carcinoma of the endometrium. , 2006, Annals of diagnostic pathology.

[11]  R. Soslow,et al.  Histologic subtypes of ovarian carcinoma: an overview. , 2008, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[12]  Zhong Jiang,et al.  The Oncofetal Protein IMP3: A Novel Biomarker for Endometrial Serous Carcinoma , 2008, The American journal of surgical pathology.

[13]  M. Nucci,et al.  Histologic and immunohistochemical decision-making in endometrial adenocarcinoma , 2008, Modern Pathology.

[14]  I. Shih,et al.  Utility of p16 Expression for Distinction of Uterine Serous Carcinomas From Endometrial Endometrioid and Endocervical Adenocarcinomas: Immunohistochemical Analysis of 201 Cases , 2009, The American journal of surgical pathology.

[15]  A. Reuss,et al.  The biological and clinical value of p53 expression in pelvic high‐grade serous carcinomas , 2010, The Journal of pathology.

[16]  L. Tafe,et al.  Endometrial and ovarian carcinomas with undifferentiated components: clinically aggressive and frequently underrecognized neoplasms , 2010, Modern Pathology.

[17]  M. Köbel,et al.  High-Grade Endometrial Carcinoma: Serous and Grade 3 Endometrioid Carcinomas Have Different Immunophenotypes and Outcomes , 2010, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[18]  Samuel Leung,et al.  Diagnosis of Ovarian Carcinoma Cell Type is Highly Reproducible: A Transcanadian Study , 2010, The American journal of surgical pathology.

[19]  R. Soslow.  Endometrial carcinomas with ambiguous features. , 2010, Seminars in diagnostic pathology.

[20]  D. Huntsman,et al.  Differences in Tumor Type in Low-stage Versus High-stage Ovarian Carcinomas , 2010, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[21]  A. Mes-Masson,et al.  Characterization of the molecular differences between ovarian endometrioid carcinoma and ovarian serous carcinoma , 2010, The Journal of pathology.

[22]  G. Sica,et al.  p53 overexpression in morphologically ambiguous endometrial carcinomas correlates with adverse clinical outcomes , 2010, Modern Pathology.

[23]  S. Wiseman,et al.  Loss of BAF250a (ARID1A) is frequent in high‐grade endometrial carcinomas , 2011, The Journal of pathology.

[24]  B. Kong,et al.  A Proposed Model for Endometrial Serous Carcinogenesis , 2011, The American journal of surgical pathology.

[25]  S. Leung,et al.  Calculator for ovarian carcinoma subtype prediction , 2011, Modern Pathology.

[26]  M. Köbel,et al.  Letter to the editor regarding ‘Roh MH, Lassin Y, Miron A et al. High-grade fimbrial-ovarian carcinomas are unified by p53, PTEN and PAX2 expression’ , 2011, Modern Pathology.

[27]  A. Mes-Masson,et al.  Subtype‐specific mutation of PPP2R1A in endometrial and ovarian carcinomas , 2011, The Journal of pathology.

[28]  Thomas Zeng,et al.  Use of mutation profiles to refine the classification of endometrial carcinomas , 2012, The Journal of pathology.

[29]  K. Garg,et al.  Strategies for Distinguishing Low-grade Endometrioid and Serous Carcinomas of Endometrium , 2012, Advances in anatomic pathology.

[30]  Dennis C. Sgroi,et al.  Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes , 2016 .

[31]  E. Pirog,et al.  The Diagnosis of Endometrial Carcinomas With Clear Cells by Gynecologic Pathologists: An Assessment of Interobserver Variability and Associated Morphologic Features , 2012, The American journal of surgical pathology.

[32]  G. Mills,et al.  Clinical Assessment of PTEN Loss in Endometrial Carcinoma: Immunohistochemistry Out-Performs Gene Sequencing , 2011, Modern Pathology.

[33]  C Blake Gilks,et al.  Poor Interobserver Reproducibility in the Diagnosis of High-grade Endometrial Carcinoma , 2013, The American journal of surgical pathology.

[34]  M. Post.  Identification of Molecular Pathway Aberrations in Uterine Serous Carcinoma by Genome-wide Analyses , 2013 .