Tumor suppressor gene, cell surface adhesion molecule, and multidrug resistance in Müllerian serous carcinomas: clinical divergence without immunophenotypic differences.
OBJECTIVE
We hypothesize that differences in the expression of selected tumor suppressor genes, cell surface adhesion molecules, and multidrug resistance glycoproteins could account for some of the reported differences between uterine serous carcinoma (USC) and extrauterine serous carcinomas (ESC), including ovarian and primary peritoneal carcinoma (OSC and PSC, respectively).


METHODS
We studied the expression of the following antigens in 20 USCs, 20 OSCs, and 10 PSCs: p53 and mdm-2 (tumor suppressor genes), CD44 and CD44v6 (cell surface adhesion molecules), and the p-glycoprotein (a multidrug resistance protein recognized by two antibodies, C494 and JSB1). We further studied chemotherapeutic drug resistance by examining reports prepared using the Oncotech Extreme Drug Resistance Assay from 24 of the 50 study patients. Clinical data were obtained from medical record review.


RESULTS
USC, OSC, and PSC patients were similar with respect to mean age at diagnosis, mean gravidity, mean parity, personal history of breast cancer, percentage treated with chemotherapy, and survival at 3 and 5 years postdiagnosis. Significant clinical differences included a high prevalence of nulliparity in OSC (P = 0.05), a low prevalence of Caucasian race in USC (P = 0.008), a paucity of stage I patients in OSC and PSC (P = 0.03), a high prevalence of familial breast cancer in OSC (P = 0.06), and superior 2-year survival in OSC (P = 0.02). Seventy-five percent of USCs, 52% of OSCs, and 60% of PSCs expressed p53. Five percent of USCs, 19% of OSCs, and 0% of PSCs expressed mdm-2. Forty percent of USCs, 33% of OSCs, and 10% of PSCs expressed CD44. None of the USCs, OSCs, or PSCs expressed CD44v6. Sixty-one percent of USCs and OSCs and 82% of PSCs expressed C494 while 17% of USCs, 19% of OSCs, and 20% of PSCs expressed JSB1. None of these apparent differences was statistically significant. USC, OSC, and PSCs patients did not demonstrate significant differences with respect to extreme drug resistance. However, the following trends were noted (P = 0.06): more prevalent low drug resistance for cyclophosphamide in OSC compared with USC and more prevalent extreme drug resistance for etoposide in OSC compared with USC.


CONCLUSIONS
Therefore, despite significant clincial differences, the USCs and ESCs in our series do not differ significantly with respect to the expression of the tumor suppressor genes, cell surface adhesion molecules, and drug resistance proteins studied. It is premature, however, to recommend that USCs and ESCs should be treated identically.
Soslow
R A
RA
Department of Pathology, Weill Medical College of Cornell University-New York Presbyterian Hospital, New York, New York 10021, USA.
Slomovitz
B M
BM
Saqi
A
A
Baergen
R N
RN
Caputo
T A
TA
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007150:Immunohistochemistry; D016130:Immunophenotyping; D008875:Middle Aged; D018200:Mixed Tumor, Mullerian / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009687:Nuclear Proteins; D010051:Ovarian Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D014594:Uterine Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D018435:ATP Binding Cassette Transporter, Subfamily B; C112697:CD44v6 antigen; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2