Arch Pathol Lab Med—Vol 131, September 2007 Endometrial-Related Cancers—Henson et al 1337 Original Articles Population-Based Analysis of Pathologic Data A New Approach to the Investigation of Uterine Endometrial and Ovarian Endometrioid Carcinomas Donald Earl Henson, MD; Arnold M. Schwartz, MD, PhD; AmyTilara, MD; Philip M. Grimley, MD; William F. Anderson, MD, MPH ● Context.—Population-based analysis of the histopathol- ogy of endometrioid adenocarcinoma of the endometrium and ovary combined with epidemiologic techniques offer a new approach to exploring the relationship of tumors that share a similar range of morphologic phenotypes. Objective.—To evaluate the contribution of the Surveil- lance, Epidemiology, and End Results database to our un- derstanding of gynecologic pathology. Specifically, to test and compare whether the etiology/pathogenesis of ovarian endometrioid cancer is as dependent upon the reproduc- tive environment as uterine endometrial carcinoma. Design.—Graphic plots of the epidemiologic patterns were analyzed relating to incidence and age-specific rates of ovarian and uterine endometrioid carcinomas. The graphic analysis included evaluation of age frequency den- sity plots and logarithmic plots (log-log) of age-specific in- cidence rates. Results.—At all ages, uterine endometrioid carcinomas have higher incidence rates than their ovarian homologues. Up to the age of 50 years, the log-log plots of age-specific incidence rates for each of these tumors remain essentially parallel. In contrast, after age 50 (menopause), the inci- dence rates begin to diverge: the rates for uterine endo- metrial carcinomas continue to rise, whereas the rates for ovarian endometrioid carcinomas plateau. This divergence persists even when the age-specific incidence is stratified according to histologic grade. Interestingly, endometrial stromal sarcomas follow an incidence rate pattern nearly identical to that of ovarian endometrioid carcinomas. Conclusions.—The continuum of cellular and molecular events predisposing to gynecologic cancers of endome- trioid phenotype apparently cease to operate in the ovary after menopause, but additional cellular and molecular events appear to occur in the ageing uterine endometrium. (Arch Pathol Lab Med. 2007;131:1337–1342) B oth the uterine mucosa and the ovary may be the site of endometrioid adenocarcinomas due to the mu ¨ lle- rian origin of their epithelium. Both organs will demon- strate an identical histopathologic pattern of their carci- nomas, and in some cases the carcinomas will be syn- chronous. In order to study the factors relating to the de- velopment and progression of these tumors, pathologists have investigated the expression of tissue- and tumor-as- sociated markers and the molecular pathways providing a growth, invasive, and metastatic advantage for these neoplasms. Pathologists have not, on the other hand, in- Accepted for publication April 3, 2007. From the George Washington University Cancer Institute, Office of Cancer Prevention and Control (Drs Henson and Tilara) and the De- partment of Pathology, George Washington University Medical Center (Dr Schwartz), Washington, DC; the Department of Pathology,The Uni- formed Services University of the Health Sciences, Bethesda, Md (Dr Grimley); and the Division of Cancer Epidemiology and Genetics, Na- tional Cancer Institute, Bethesda, Md (Dr Anderson). Dr Tilara is cur- rently with the Department of Internal Medicine, New York Presbyte- rian Hospital, Weill Cornell Medical College, New York. The authors have no relevant financial interest in the products or companies described in this article. This was an oral presentation at the 2006 Annual Meeting of the United States and Canadian International Academy of Pathology, At- lanta, Ga, February 2006. Reprints: Donald Earl Henson, MD, George Washington University Cancer Institute, Ross Hall, Room 502, 2300 Eye St, NW, Washington, DC 20037 (e-mail: patdeh@gwumc.edu). vestigated the population dynamics and age-related fac- tors that may provide insight into the comparative carci- nogeneses of these two tumor types that have identical histopathologic patterns but derive from different organs. The combination of epidemiologic assessment and patho- logic analysis imparts additional information supporting cellular and molecular events and provides new data for hypothesis testing. In 1954, Armitage and Doll 1,2 demonstrated that the age- specific incidence rates of certain epithelial cancers have a linear slope when plotted against the age of diagnosis on logarithmic scales. This logarithmic transformation of population data confirmed a theoretical equation relating the development of carcinoma to a series of cellular events, thereby supporting the multistage process of carcinogen- esis with a continuous increase in cancer rate as a function of age. 3 Many epidemiologists have since exploited loga- rithmically scaled plots to investigate both the origins and rates of human cancer. 4–6 We hypothesized that overall population-based age-in- cidence patterns could yield additional insights into can- cer etiology/pathogenesis if coupled with histopathologic observations. Until the current era of electronic data col- lection and informatics, such a task was formidable. The difficulty in acquiring quantitatively significant morpho- logic data at the population level led investigators to rely upon observations from case-controlled studies. This em- pirical approach has made it difficult to exclude institu-