Progressive dysregulation of proliferation during cervical carcinogenesis as measured by MPM-2 antibody staining.
To better characterize the amount and location of loss of proliferation control during cervical carcinogenesis, 44 cervical cone biopsy specimens containing various grades of premalignant and malignant lesions and 12 normal cervix specimens were immunohistochemically examined using MPM-2. This antibody recognizes a phosphorylated epitope on a group of proteins that are preferentially phosphorylated at mitosis. The spatial organization of mitotic figures was determined using a computer-assisted image analysis system. The mitotic figure frequencies/unit of epithelial area were found to increase as the histological type progressed; the numbers of mitoses/square millimeter was 1.7 +/- 0.5 (mean +/- SE) for control normal epithelium (n = 12), 3.1 +/- 1.7 for normal epithelium adjacent to cervical intraepithelial neoplasia (CIN) and cancer (n = 28), 7.9 +/- 1.3 for CIN1 (n = 24), 75.8 +/- 16.3 for CIN2 (n = 11), 127.2 +/- 9.7 for CIN3 (n = 22), 196.9 +/- 33.2 for carcinoma in situ (n = 9), and 156.2 +/- 31.0 for cervical carcinoma (n = 8). The MPM-2 index was higher in high-risk premalignant lesions (i.e., those adjacent to areas of high-grade CIN and carcinoma) than it was in lower risk premalignant lesions (i.e., those with no adjacent higher grade CIN or cervical cancer), even if they exhibited the same histological grade. Moreover, the mean relative distance of the mitotic cells from the basement membrane (i.e., the distance from the basal layer to the surface) also increased as the histological grade progressed. These results suggest that proliferation becomes sequentially dysregulated both quantitatively and spatially during cervical carcinogenesis and that the MPM-2 antibody might be useful as a proliferation biomarker.
Hu
W
W
Department of Gynecologic Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Mitchell
M F
MF
Boiko
I V
IV
Linares
A
A
Kim
H G
HG
Malpica
A
A
Tortolero-Luna
G
G
Hittelman
W N
WN
D000911:Antibodies, Monoclonal; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D002455:Cell Division; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008940:Mitotic Index; D017346:Protein Serine-Threonine Kinases / Q000276:immunology* / Q000378:metabolism; D002578:Uterine Cervical Dysplasia / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure
D000911:Antibodies, Monoclonal; D017346:Protein Serine-Threonine Kinases