Histotype-genotype correlation in 36 high-grade endometrial carcinomas.
Endometrioid, serous, and clear cell carcinomas are the major types of endometrial carcinoma. Histologic distinction between these different tumor types can be difficult in high-grade cases, in which significant interobserver diagnostic disagreement exists. Endometrioid and clear cell carcinomas frequently harbor ARID1A and/or PTEN mutations. Serous carcinoma acquires TP53 mutations/inactivation at onset, with a significant subset harboring an additional mutation in PPP2R1A. This study examines the correlation between tumor histotype and genotype in 36 previously genotyped high-grade endometrial carcinomas. This included 23 endometrioid/clear cell genotype and 13 serous genotype tumors. Eight subspecialty pathologists reviewed representative online slides and rendered diagnoses before and after receiving p53, p16, and estrogen receptor immunostaining results. κ statistics for histotype-genotype concordance were calculated. The average κ values for histotype-genotype concordance was 0.55 (range, 0.30 to 0.67) on the basis of morphologic evaluation alone and it improved to 0.68 (range, 0.54 to 0.81) after immunophenotype consideration (P<0.001). Genotype-incompatible diagnoses were rendered by at least 2 pathologists in 12 of 36 cases (33%) (3 cases by 2/8 pathologists, 2 by 3/8, 2 by 4/8, 3 by 6/8, 1 by 7/8, and 1 case by 8/8 pathologists). Six of the 12 were endometrioid/clear cell genotype tumors, and the other 6 were serous genotype tumors. The histopathologic features associated with histotype-genotype-discordant cases were reviewed, and specific diagnostic recommendations were made to improve concordance. This study found that although the majority of morphologic diagnoses are genotype concordant, genotype-incompatible diagnoses are made in a significant subset of cases. Judicious use and interpretation of p53 immunohistochemistry in selected scenarios can improve histotype-genotype concordance.
Departments of *Pathology and Laboratory Medicine ¶Gynecology and Obstetrics, University of British Columbia †Genetic Pathology Evaluation Center, Vancouver General Hospital, Vancouver, BC ‡Department of Pathology, University of Calgary, Calgary, AB §Department of Pathology, University of Toronto, Toronto, ON, Canada ∥Department of Pathology, Faculty of Medicine, Norwegian Radium Hospital, University of Oslo, Oslo, Norway #Department of Pathology, Massachusetts General Hospital **Department of Pathology, Brigham and Women's Hospital, Boston, MA ††Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY.
Lien N
LN
Hoang
Melissa K
MK
McConechy
Martin
M
Köbel
Guangming
G
Han
Marjan
M
Rouzbahman
Ben
B
Davidson
Julie
J
Irving
Rola H
RH
Ali
Sam
S
Leung
Jessica N
JN
McAlpine
Esther
E
Oliva
Marisa R
MR
Nucci
Robert A
RA
Soslow
David G
DG
Huntsman
C Blake
CB
Gilks
Cheng-Han
CH
Lee
D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001706:Biopsy; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D016889:Endometrial Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000235:genetics / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics; D015588:Observer Variation; D051059:PTEN Phosphohydrolase / Q000235:genetics; D010641:Phenotype; D011237:Predictive Value of Tests; D054648:Protein Phosphatase 2 / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis; D015203:Reproducibility of Results; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
C112476:ARID1A protein, human; D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C517191:PPP2R1A protein, human; D011960:Receptors, Estrogen; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D054648:Protein Phosphatase 2; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human