FCCC LOGO Faculty Publications
Roland IH , Yang WL , Yang DH , Daly MB , Ozols RF , Hamilton TC , Lynch HT , Godwin AK , Xu XX
Loss of surface and cyst epithelial basement membranes and preneoplastic morphologic changes in prophylactic oophorectomies
Cancer. 2003 Dec;98(12) :2607-2623
Back to previous list
BACKGROUND. The authors suggested that the loss of collagen IV and laminin-containing basement membrane and the loss of Disabled-2 (Dab2) expression were two critical events associated with morphologic dysplastic changes of the ovarian surface epithelium as a step in tumorigenicity. Both the basement membrane and Dab2, a candidate tumor suppressor of ovarian carcinoma, were involved in epithelial cell surface positioning and organization. The authors speculated that the purging of the basement membrane may be similar to the proteolysis during gonadotropin-stimulated ovulation, a cyclooxygenase 2 (Cox-2)-mediated process. METHODS. Prophylactic oophorectomy is used to prevent breast and ovarian carcinoma in high-risk populations. These ovarian tissue specimens often contain an increased presence of morphologically abnormal lesions that are believed to be preneoplastic. The authors evaluated archived prophylactic oophorectomy specimens to verify whether the loss of Dab2 expression and the removal of the basement membrane that occur at the ovarian surface and inclusion cyst epithelia are molecular markers of preneoplastic lesions. Of the 36 samples containing identifiable ovarian surface epithelial components on slides, immunostaining was employed to evaluate the intactness of the basement membrane (periodic acid-Schiff [PAS1, collagen IV, and laminin) and the expression of Dab2 and Cox-2. Expression of Cox-1 and Cox-2 also were evaluated in cultured ovarian surface epithelial cells prepared from ovarian tissue specimens removed from patients who underwent prophylactic surgery. RESULTS. The morphologically normal ovarian surface epithelium typically contained a collagen IV- and laminin-positive basement membrane, which also was detected by PAS staining. Many morphologically altered areas, such as papillomatosis, invaginations, inclusion cysts, stratification, adenomas, and microscopic adenocarcinomas, were found in these specimens. Both the morphologically altered and adjacent morphologically normal epithelia consistently exhibited loss of basement membrane and/or Dab2 expression and an increase in Cox-2 staining. Frequently, an increase in Cox-2 staining was correlated with the loss of epithelial basement membrane in morphologically normal areas. CONCLUSIONS. The loss of Dab2 and basement membrane and the overexpression of Cox-2 were observed in presumptive neoplastic precursor areas of oophorectomy specimens obtained from a population at high risk for ovarian carcinoma. Transient loss of collagen IV and laminin in the basement membrane of the preneoplastic epithelium and the loss of Dab2 expression are common early events associated with morphologic alteration and tumorigenicity of the ovarian surface epithelium. The authors concluded that Cox-2 overexpression may play a role in the purging of basement membrane of the ovarian surface epithelium, mimicking the process of ovulation. Further experiments may be able to test the hypothetical model derived from these histologic observations. (C) 2003 American Cancer Society.
English Article Xu, XX; *Fox* *Chase* Canc Ctr, Ovarian Canc Program, 7701 Burholme Ave, Philadelphia, PA 19111 USA. Research Addresses: *Fox* *Chase* Canc Ctr, Ovarian Canc Program, Philadelphia, PA 19111 USA. Creighton Univ, Dept Prevent Med & Publ Hlth, Omaha, NE 68178 USA. Cited References: AOKI Y, 2000, J REPROD MED, V45, P159 AUERSPERG N, 2001, ENDOCR REV, V22, P255 BARAKAT RR, 2000, CANCER, V89, P383 BAST RC, 1993, CANCER, V71, P1597 BELL DA, 1994, CANCER, V73, P1859 BERCHUCK A, 1993, CANCER, V71, P545 BISSELL MJ, 1987, J CELL SCI S, V8, P327 CAPOCHICHI CD, 2002, CANCER, V95, P1802 CRAMER DW, 1983, J NATL CANCER I, V71, P717 DANNENBERG AJ, 2001, LANCET ONCOL, V2, P544 DAVIS BJ, 1999, ENDOCRINOLOGY, V140, P2685 DELIGDISCH L, 1999, CANCER, V86, P1544 DENKERT C, 2002, AM J PATHOL, V160, P893 DENNEFORS B, 1982, PROSTAGLANDINS, V24, P295 DOWNS SM, 1982, AM J ANAT, V164, P265 DOWNS SM, 1983, ANAT REC, V205, P159 DUFFY DM, 2001, MOL HUM REPROD, V7, P731 EGEBLAD M, 2002, NAT REV CANCER, V2, P161 FATHALLA MF, 1971, LANCET, V2, P163 FAZILI Z, 1999, ONCOGENE, V18, P3104 FEARON ER, 1990, CELL, V61, P759 FEELEY KM, 2001, HISTOPATHOLOGY, V38, P87 FERRANDINA G, 2002, GYNECOL ONCOL, V85, P305 FERRANDINA G, 2002, ANN ONCOL, V13, P1205 GODWIN AK, 1993, CANCER, V71, P530 GODWIN AK, 1992, J NATL CANCER I, V84, P592 GUPTA RA, 2003, CANCER RES, V63, P906 HABER D, 2002, NEW ENGL J MED, V346, P1660 HAGIOS C, 1998, PHILOS T ROY SOC B, V353, P857 HAMILTON TC, 1998, CANC TREAT RES, V95, P103 HOSKINS WJ, 1996, J NATL CANCER I, V88, P1790 HOWE LR, 2002, SEMIN ONCOL S11, V29, P111 IVARSSON K, 2001, HUM REPROD, V16, P18 KLIMP AH, 2001, CANCER RES, V61, P7305 KNUDSON AG, 2001, NAT REV CANCER, V1, P157 LAL G, 2001, CANCER RES, V61, P6131 LANGENBACH R, 1995, CELL, V83, P483 LEAHY KM, 2002, CANCER RES, V62, P625 LEMAIRE WJ, 1989, STEROIDS, V54, P455 LIM H, 1997, CELL, V91, P197 LIU CH, 2001, J BIOL CHEM, V276, P18563 MAHLER JF, 1996, TOXICOL PATHOL, V24, P717 MASFERRER JL, 2000, CANCER RES, V60, P1306 MATRISIAN LM, 1999, CURR BIOL, V9, P776 MATSUMOTO Y, 2001, INT J MOL MED, V8, P31 MISHRA SK, 2002, EMBO J, V21, P4915 MOK SC, 1998, ONCOGENE, V16, P2381 MOORE BC, 2000, CURR MED CHEM, V7, P1131 MUNKARAH AR, 2002, J SOC GYNECOL INVEST, V9, P168 NASI ML, 2002, ANN ONCOL, V13, P1169 NORMAN RJ, 2001, LANCET, V358, P1287 OKAMURA H, 2001, IT J ANAT EMBRYOL, V106, P263 OKAMURA H, 1985, ADV PROSTAGLANDIN TH, V15, P597 OSHIMA M, 1996, CELL, V87, P803 OZOLS RF, 2003, GYNECOL ONCOL, V88, PS67 OZOLS RF, 2003, GYNECOL ONCOL 2, V88, PS59 PALL M, 2001, HUM REPROD, V16, P1323 REESE J, 2001, ENDOCRINOLOGY, V142, P3198 RIMAN T, 1998, CLIN ENDOCRINOL, V49, P695 RODRIGUEZBURFORD C, 2002, CLIN CANCER RES, V8, P202 RUDOLPHOWEN LA, 1998, CANCER RES, V58, P5500 SALAZAR H, 1996, J NATL CANCER I, V88, P1810 SCULLY RE, 1995, J CELL BIOCHEM S, V23, P208 SHENG ZJ, 2000, ONCOGENE, V19, P4847 SHIGEMASA K, 2003, INT J ONCOL, V22, P99 SMITH WL, 1996, J BIOL CHEM, V271, P33157 STEINBACH G, 2000, NEW ENGL J MED, V342, P1946 STERNLICHT MD, 1999, CELL, V98, P137 SYED V, 2001, CANCER RES, V61, P6768 SYMPSON CJ, 1995, SEMIN CANCER BIOL, V6, P159 TALBOT P, 1987, GAMETE RES, V17, P287 TESTA JR, 1994, CANCER RES, V54, P2778 TIMPL R, 1986, INT REV EXP PATHOL, V29, P1 TOKUYAMA O, 2001, INT J MOL MED, V8, P603 TSAFRIRI A, 1999, EXP CLIN ENDOCR DIAB, V107, P1 WERNESS BA, 1999, HUM PATHOL, V30, P151 WILLIAMS CS, 2000, CANCER RES, V60, P6045 YANG DH, 2002, CANCER, V94, P2380 YANG DH, 2002, DEV BIOL, V251, P27 ZHENG WX, 2000, GYNECOL ONCOL, V76, P80 Number of cited references: 80 Number of times cited: 0 Publisher: JOHN WILEY & SONS INC; 111 RIVER ST, HOBOKEN, NJ 07030 USA. 0008-543X