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Christopher Paul Crum, MD
Senior Pathologist, Brigham and Women's Hospital
Professor of Pathology, Harvard Medical School

Brigham and Women's Hospital
Department of Pathology
75 Francis Street
Boston, MA 02115


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Research Narrative:

Our laboratory focuses on the pathobiology of cancer precursors in the female genital tract. These include pre-invasive neoplasms of the vulva, cervix, endometrium and distal fallopian tube. Lately our interests have centered on the novel concept that pelvic serous cancer, the most lethal "ovarian" cancer in women, arises in many instances from the distal fallopian tube. We have shown that a very high percentage of serous cancers arising in women with BRCA mutations emerge from the tubal fimbria and that the distal tube is a source for pelvic cancer in one half of women for whom BRCA status is unknown. A striking biologic alteration that occurs in normal appearing tubal mucosa and shares many features with serous cancer, termed the tubal "p53 signature", was described in our laboratory, and has emerged as the leading candidate precursor to pelvic serous cancer. We have recently shown that this precursor shares risk factors with ovarian cancer, strengthening further its status as an important early event in serous carcinogenesis. This discovery is the subject of several collaborative projects designed to determine 1) if the p53 signature is a surrogate risk factor for serous malignancy, 2) if it predates the malignancy, 3) the extent to which early malignancies arising in the fallopian tube contribute to tumors otherwise classified as ovarian or peritoneal serous carcinomas and 4) the biologic events that characterize precursor development and its transition to malignancy in women with BRCA mutations and the general population. Our hope is that a fully characterized precursor to pelvic serous cancer will encourage new directions in ovarian/fallopian tube detection and prevention


Education:
MD

Lab Members:
Wa Xian, PhD, Postdoctoral Research Fellow
Karishma Mehra, MD, Postdoctoral Research Fellow
Mitra Mehtrad, MD, Research Fellow
Eleanor Chen, MD, PhD, Clinical Fellow

Publications (Pulled from Harvard Catalyst Profiles):

1. Meserve EE, Strickland KC, Miron A, Soong TR, Campbell F, Howitt BE, Crum CP. Evidence of a Monoclonal Origin for Bilateral Serous Tubal Intraepithelial Neoplasia. Int J Gynecol Pathol. 2019 Sep; 38(5):443-448.

2. Liu MZ, Hung YP, Huang EC, Howitt BE, Nucci MR, Crum CP. HPV 6-associated HSIL/Squamous Carcinoma in the Anogenital Tract. Int J Gynecol Pathol. 2019 Sep; 38(5):493-497.

3. Ditzel HM, Strickland KC, Meserve EE, Stover E, Konstantinopoulos PA, Matulonis UA, Muto MG, Liu JF, Feltmate C, Horowitz N, Berkowitz RS, Gupta M, Hecht JL, Lin DI, Jochumsen KM, Welch WR, Hirsch MS, Quade BJ, Lee KR, Crum CP, Mutter GL, Nucci MR, Howitt BE. Assessment of a Chemotherapy Response Score (CRS) System for Tubo-Ovarian High-Grade Serous Carcinoma (HGSC). Int J Gynecol Pathol. 2019 May; 38(3):230-240.

4. Watkins JC, Yang E, Crum CP, Herfs M, Gheit T, Tommasino M, Nucci MR. Classic Vulvar Intraepithelial Neoplasia With Superimposed Lichen Simplex Chronicus: A Unique Variant Mimicking Differentiated Vulvar Intraepithelial Neoplasia. Int J Gynecol Pathol. 2019 Mar; 38(2):175-182.

5. Stewart CJR, Crum CP, McCluggage WG, Park KJ, Rutgers JK, Oliva E, Malpica A, Parkash V, Matias-Guiu X, Ronnett BM. Guidelines to Aid in the Distinction of Endometrial and Endocervical Carcinomas, and the Distinction of Independent Primary Carcinomas of the Endometrium and Adnexa From Metastatic Spread Between These and Other Sites. Int J Gynecol Pathol. 2019 Jan; 38 Suppl 1:S75-S92.

6. Murali R, Davidson B, Fadare O, Carlson JA, Crum CP, Gilks CB, Irving JA, Malpica A, Matias-Guiu X, McCluggage WG, Mittal K, Oliva E, Parkash V, Rutgers JKL, Staats PN, Stewart CJR, Tornos C, Soslow RA. High-grade Endometrial Carcinomas: Morphologic and Immunohistochemical Features, Diagnostic Challenges and Recommendations. Int J Gynecol Pathol. 2019 Jan; 38 Suppl 1:S40-S63.

7. Xian W, Duleba M, Zhang Y, Yamamoto Y, Ho KY, Crum C, McKeon F. The Cellular Origin of Barrett's Esophagus and Its Stem Cells. Adv Exp Med Biol. 2019; 1123:55-69.

8. Soong TR, Dinulescu DM, Xian W, Crum CP. Frontiers in the Pathology and Pathogenesis of Ovarian Cancer: Cancer Precursors and "Precursor Escape". Hematol Oncol Clin North Am. 2018 12; 32(6):915-928.

9. Soong TR, Howitt BE, Horowitz N, Nucci MR, Crum CP. The fallopian tube, "precursor escape" and narrowing the knowledge gap to the origins of high-grade serous carcinoma. Gynecol Oncol. 2019 02; 152(2):426-433.

10. Soong TR, Kolin DL, Teschan NJ, Crum CP. Back to the Future? The Fallopian Tube, Precursor Escape and a Dualistic Model of High-Grade Serous Carcinogenesis. Cancers (Basel). 2018 Nov 28; 10(12).