Cervical squamocolumnar junction-specific markers define distinct, clinically relevant subsets of low-grade squamous intraepithelial lesions.
Low-grade cervical squamous abnormalities (low-grade squamous intraepithelial lesions [LSIL, CIN1]) can be confused with or followed by high-grade (HSIL, CIN2/3) lesions, expending considerable resources. Recently, a cell of origin for cervical neoplasia was proposed in the squamocolumnar junction (SCJ); HSILs are almost always SCJ, but LSILs include SCJ and SCJ subsets. Abnormal cervical biopsies from 214 patients were classified by 2 experienced pathologists (panel) as LSIL or HSIL using published criteria. SILs were scored SCJ and SCJ using SCJ-specific antibodies (keratin7, AGR2, MMP7, and GDA). Assessments of interobserver agreement, p16 staining pattern, proliferative index, and outcome were compared. The original diagnostician agreed with the panel diagnosis of HSIL and SCJ LSIL in all cases (100%). However, for SCJ LSIL, panelists disagreed with each other by 15% and with the original diagnostician by 46.2%. Comparing SCJ and SCJ LSILs, 60.2% and 94.9% were p16 positive, 23% and 74.4% showed strong (full-thickness) p16 staining, and 0/54 (0%) and 8/33 (24.2%) with follow-up had an HSIL outcome, respectively. Some SCJ LSILs are more likely to both generate diagnostic disagreement and be associated with HSIL. Conversely, SCJ LSILs generate little observer disagreement and, when followed, have a very low risk of HSIL outcome. Thus, SCJ biomarkers in conjunction with histology may segregate LSILs with very low risk of HSIL outcome and conceivably could be used as a management tool to reduce excess allocation of resources to the follow-up of these lesions.
*Department of Pathology, Division of Women's and Perinatal Pathology §Department of Obstetrics and Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, MA ‡Department of Pathology, Cedar Sinai Medical Center, Los Angeles, CA †Department of Pathology, GIGA-Cancer, University of Liege, Liege, Belgium ∥Genome Institute of Singapore, ASTAR The Jackson Laboratory for Genomic Medicine, CT ¶The Jackson Laboratory for Genomic Medicine, The University of Connecticut School of Medicine, CT.
Michael
M
Herfs
Carlos
C
Parra-Herran
Brooke E
BE
Howitt
Anna R
AR
Laury
Marisa R
MR
Nucci
Sarah
S
Feldman
Cynthia A
CA
Jimenez
Frank D
FD
McKeon
Wa
W
Xian
Christopher P
CP
Crum
D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D060787:Neoplasm Grading; D018307:Neoplasms, Squamous Cell / Q000737:chemistry* / Q000473:pathology; D015588:Observer Variation; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000737:chemistry* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000737:chemistry* / Q000473:pathology
D014408:Biomarkers, Tumor