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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 pathogenesis of gynecologic cancer and how it informs strategies for prevention. In the past two decades we have focused on cervical and ovarian carcinogenesis. In 2012 we described a putative cell of origin for cervical carcinoma in the squamo columnar junction (SCJ) and in subsequent publications postulated that pre-emptive cryoablation of the SCJ cells would lower the risk of cervical cancer. This concept is currently being tested in an ongoing clinical trial sponsored by the IARC/WHO. Our interests have centered on the novel concept that high-grade pelvic serous cancer, the most lethal "ovarian" cancer in women, arises from the distal fallopian tube. In 2005 we developed the SEE-FIM dissection protocol for examination of the fallopian tubes in women with germ-line BRCA mutations. This protocol, when applied to both low and high risk women revealed the presence of not only early carcinomas but a spectrum of “early serous precursors” (ESPs) in the fimbria, further linking the tube to serous cancer. We hypothesized that disseminated serous cancer arises not only via 1) the development of an early tubal cancer that subsequently metastasizes, but also 2) via detachment of precursor cells that subsequently become malignant in the peritoneal cavity (precursor escape). We have several funded studies in progress to 1) establish a stronger association between ESPs and concurrent disseminated malignancies, 2) determine if ESPs from both uterus and fallopian tube contribute to eventual serous carcinomas, and 3) track the evolution from ESP to cancer in the peritoneal cavity.  Currently, opportunistic salpingectomy is being practiced as a strategy to potentially lower the incidence rate of serous cancer. Our goal is to develop a clearer picture of the molecular and physical landscape integral to cancer development to complete this narrative and address novel strategies in serous cancer 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

Additional News:



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).