Diagnosis of Ovarian Carcinoma Cell Type is Highly Reproducible: A Transcanadian Study

Reproducible diagnosis of ovarian carcinoma cell types is critical for cell type-specific treatment. The purpose of this study was to test the reproducibility of cell type diagnosis across Canada. Analysis of the interobserver reproducibility of histologic tumor type was performed among 6 pathologists after brief training in the use of modified World Health Organization criteria to classify ovarian carcinomas into 1 of 6 categories: high-grade serous, endometrioid, clear cell, mucinous, low-grade serous, and other. These 6 pathologists independently reviewed a test set of 40 ovarian carcinomas. A validation set of 88 consecutive ovarian carcinomas drawn from 5 centers was subject to local review by 1 of the 6 study pathologists, and central review by a single observer. Interobserver agreement was assessed through calculation of concordance and κ values for pair-wise comparison. For the test set, the paired concordance between pathologists in cell type diagnosis ranged from 85.0% to 97.5% (average 92.3%), and the κ values were 0.80 to 0.97 (average 0.89). Inclusion of immunostaining results did not significantly improve reproducibility (P=0.69). For the validation set, the concordance between original diagnosis and local review was 84% and between local review and central review was 94%. The κ values were 0.73 and 0.89, respectively. With a brief training exercise and the use of defined criteria for ovarian carcinoma subtyping, there is excellent interobserver reproducibility in diagnosis of cell type. This has implications for clinical trials of subtype-specific ovarian carcinoma treatments.

[1]  M. Duggan,et al.  Pathology reviews in the research context: future directions. , 2010, Surgery.

[2]  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.

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

[4]  D. Huntsman,et al.  Tumor type and substage predict survival in stage I and II ovarian carcinoma: insights and implications. , 2010, Gynecologic oncology.

[5]  Anna Adamiak,et al.  HER2 overexpression and amplification is present in a subset of ovarian mucinous carcinomas and can be targeted with trastuzumab therapy , 2009, BMC Cancer.

[6]  C. Gilks,et al.  Ovarian carcinoma pathology and genetics: recent advances. , 2009, Human pathology.

[7]  D. Huntsman,et al.  A Limited Panel of Immunomarkers Can Reliably Distinguish Between Clear Cell and High-grade Serous Carcinoma of the Ovary , 2009, The American journal of surgical pathology.

[8]  A. Parwani Tumor cell type can be reproducibly diagnosed and is of independent prognostic significance in patients with maximally debulked ovarian carcinoma , 2009 .

[9]  S. Leung,et al.  Ovarian Carcinoma Subtypes Are Different Diseases: Implications for Biomarker Studies , 2008, PLoS medicine.

[10]  I. Shih,et al.  Subdividing Ovarian and Peritoneal Serous Carcinoma Into Moderately Differentiated and Poorly Differentiated Does not Have Biologic Validity Based on Molecular Genetic and In Vitro Drug Resistance Data , 2008, The American journal of surgical pathology.

[11]  D. Huntsman,et al.  Critical molecular abnormalities in high-grade serous carcinoma of the ovary , 2008, Expert Reviews in Molecular Medicine.

[12]  S. Leung,et al.  Mixed Ovarian Epithelial Carcinomas With Clear Cell and Serous Components are Variants of High-grade Serous Carcinoma: An Interobserver Correlative and Immunohistochemical Study of 32 Cases , 2008, The American journal of surgical pathology.

[13]  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.

[14]  Ie-Ming Shih,et al.  Pathogenesis of Ovarian Cancer: Lessons From Morphology and Molecular Biology and Their Clinical Implications , 2008, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[15]  P. Spellman,et al.  Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities , 2008, BMC Cancer.

[16]  K. Ogawa,et al.  Postoperative whole abdominal radiotherapy in clear cell adenocarcinoma of the ovary. , 2007, Gynecologic oncology.

[17]  W. McCluggage,et al.  My approach to and thoughts on the typing of ovarian carcinomas , 2007, Journal of Clinical Pathology.

[18]  Mark F. Munsell,et al.  Interobserver and Intraobserver Variability of a Two-tier System for Grading Ovarian Serous Carcinoma , 2007, The American journal of surgical pathology.

[19]  Jane Fountain,et al.  Summary and discussion of session recommendations. , 2006, Gynecologic oncology.

[20]  S. Hauptmann,et al.  Ezrin expression is related to poor prognosis in FIGO stage I endometrioid carcinomas , 2006, Modern Pathology.

[21]  L. Cope,et al.  Patterns of p53 Mutations Separate Ovarian Serous Borderline Tumors and Low- and High-grade Carcinomas and Provide Support for a New Model of Ovarian Carcinogenesis: A Mutational Analysis With Immunohistochemical Correlation , 2005, The American journal of surgical pathology.

[22]  I. Shih,et al.  Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. , 2004, The American journal of pathology.

[23]  Michael T Deavers,et al.  Grading Ovarian Serous Carcinoma Using a Two-Tier System , 2004, The American journal of surgical pathology.

[24]  W. McCluggage,et al.  WT‐1 assists in distinguishing ovarian from uterine serous carcinoma and in distinguishing between serous and endometrioid ovarian carcinoma , 2004, Histopathology.

[25]  I. Shih,et al.  Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma. , 2003, Journal of the National Cancer Institute.

[26]  I. Jacobs,et al.  Histopathologic Features of Genetically Determined Ovarian Cancer , 2002, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[27]  Kathleen R. Cho,et al.  Gene expression in ovarian cancer reflects both morphology and biological behavior, distinguishing clear cell from other poor-prognosis ovarian carcinomas. , 2002, Cancer research.

[28]  I. Shih,et al.  Diverse tumorigenic pathways in ovarian serous carcinoma. , 2002, The American journal of pathology.

[29]  S. Tsugane,et al.  Observer disagreement in histological classification of ovarian tumors in Japan. , 1994, Gynecologic oncology.

[30]  B. Lund,et al.  Reproducibility of histopathological evaluation in epithelial ovarian carcinoma. Clinical implications , 1991, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[31]  H. Stalsberg,et al.  Observer variation in histologic classification of malignant and borderline ovarian tumors. , 1988, Human pathology.

[32]  T. Ulbright,et al.  Evaluation of the reproducibility of the World Health Organization classification of common ovarian cancers. With emphasis on methodology. , 1987, Archives of pathology & laboratory medicine.

[33]  T. Parmley,et al.  Interobserver variability in the interpretation of epithelial ovarian cancer. , 1984, Gynecologic oncology.