Christopher P. Crum, MD
Professor of Pathology (HMS) and Director, Women’s and Perinatal Pathology
Brigham and Women’s Hospital
Professor, Department of Pathology
Harvard Medical School
West Plaza (Amory Lab Building), AL-3-127
Brigham & Women's Hospital
75 Francis St.
Boston, MA 02115
Our most recent studies have concentrated on a novel pathway and precursor lesion for ovarian serous carcinogenesis that arises in the distal fallopian tube. Recognizing that women with mutations in BRCA1 or BRCA2 are at risk for both tubal and ovarian cancer, we have been testing the hypothesis that many cases of the most lethal form of ovarian cancer – ovarian surface or peritoneal serous carcinoma – originate from the tubal fimbria. To do so, we developed a protocol for sectioning and extensively examining the fimbriated end (SEE-FIM). Initial studies of BRCA+ women indicate that the majority of cancers detected in prophylactic salpingo-oophorectomy specimens originate from this location, and have been corroborated in collaborative follow-up studies (Medieros et al 2006, Callahan et al 2007). We have identified early tubal cancers in approximately one-half of women with peritoneal and ovarian serous carcinomas (irrespective of BRCA status) and have proposed the fimbria as the origin for these tumors (Kindelberger et al 2007, Carlson, Miron et al, in press). Recently, we characterized a novel precursor to pelvic serous carcinoma that is present in benign appearing mucosa in the distal fallopian tube, which we term the “p53 signature” (Lee, Miron et al, 2007). From this collection of data, we have formulated a “Serous carcinogenic sequence in the distal fallopian tube (Jarboe et al 2008). In collaboration with Drs. Shelley Tworoger, Daniel Cramer and Judy Garber, we are showing for the first time that the tubal p53 signature shares several risk factors with ovarian cancer, further supporting its role as a precursor to or surrogate marker for, pelvic serous cancer. We intend to further characterize this entity and target the serous carcinogenic sequence for early detection and possibly, prevention. This work has been supported by the existing ovarian cancer SPORE (Daniel Cramer PI) and grants from the National Cancer Institute and Columbia Hospital for Women Research Foundation (C. Crum).
Medeiros F, Muto MG, Lee Y, Elvin JA, Callahan MJ, Feltmate C, Garber JE, Cramer DW, Crum CP. The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome. Am J Surg Pathol. 2006;30:230-6.
Suh EK, Yang A, Kettenbach A, Bamberger C, Michaelis AH, Zhu Z, Elvin JA, Bronson RT, Crum CP, McKeon F. p63 protects the female germ line during meiotic arrest. Nature. 2006;444:624-8.
Senoo M, Pinto F, Crum CP, McKeon F. p63 Is essential for the proliferative potential of stem cells in stratified epithelia. Cell. 2007;129:523-36
Kindelberger DW, Lee Y, Miron A, Hirsch MS, Feltmate C, Medeiros F, Callahan MJ, Garner EO, Gordon RW, Birch C, Berkowitz RS, Muto MG, Crum CP. Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: Evidence for a causal relationship. Am J Surg Pathol. 2007;31:161-9.
Folkins AK, Jarboe EA, Salemuddin A, Lee Y, Drapkin R, Garber J, Muto M, Tworoger S, Crum CP. A candidate precursor to pelvic serous cancer (p53 Signature) and its prevalence in ovaries and fallopian tubes from women with heterozygous BRCA Mutations. Gynecol Oncol, 2008 in press.
Carlson JW, Miron A, Jarboe E, Parast MM, Hirsch MS, Lee Y, Kindelberger D, Muto M, Crum CP. Serous Tubal Intraepithelial Carcinoma (STIC): Its Potential Role in Primary Peritoneal Serous Carcinoma (PPSC) and Serous Cancer Prevention. J Clin Oncol, in press
Lee Y, Miron A, Drapkin R, Nucci MR, Medeiros F, Saleemuddin A, Garber J, Birch C, Mou H, Gordon RW, Cramer DW, McKeon FD, Crum CP. A candidate precursor to serous carcinoma that originates in the distal fallopian tube. J Pathol. 2007 Jan;211(1):26-35.
Jarboe E, Folkins A, Nucci MR, Kindelberger D, Drapkin R, Miron A, Lee Y, Crum CP. Serous carcinogenesis in the fallopian tube: a descriptive classification. Int J Gynecol Pathol. 2008;27:1-9
Kindelberger DW, Lee Y, Miron A, Hirsch MS, Feltmate C, Medeiros F, Callahan MJ, Garner EO, Gordon RW, Birch C, Berkowitz RS, Muto MG, Crum CP. Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: Evidence for a causal relationship. Am J Surg Pathol. 2007 Feb;31(2):161-9.
Callahan MJ, Crum CP, Medeiros F, Kindelberger DW, Elvin JA, Garber JE, Feltmate CM, Berkowitz RS, Muto MG. Primary fallopian tube malignancies in BRCA-positive women undergoing surgery for ovarian cancer risk reduction. J Clin Oncol. 2007;25:3985-90
Crum CP, Drapkin R, Miron A, Ince TA, Muto M, Kindelberger DW, Lee Y. The distal fallopian tube: a new model for pelvic serous carcinogenesis. Curr Opin Obstet Gynecol. 2007;19:3-9.
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