Anatomic Abstracts

April 2007

Editor:
Michael Cibull, MD
Melissa Kesler, MD

CD200: a new prognostic factor in multiple myeloma
Cytokeratins 7 and 20 in primary and secondary ovarian mucinous tumors
Prognostic role of a gene signature from tumorigenic breast cancer cells

CD200: a new prognostic factor in multiple myeloma

Using Affymetrix microarrays, the authors identified expression of the CD200 gene in the multiple myeloma cells of 112 patients with newly diagnosed multiple myeloma. The CD200 gene was absent in 22 percent of multiple myeloma cells (MMCs) and present in 78 percent of MMCs. The CD200 gene was not expressed in other cells of the patients’ bone marrow. CD200 is a membrane glycoprotein that imparts an immunoregulatory signal through CD200R, leading to suppression of T-cell-mediated immune responses. Patients with CD200(absent) MMCs have an increased event-free survival (24 months) compared with patients with CD200(present) MMCs (14 month) after high-dose therapy and stem cell transplantation. In a Cox proportional hazard model, the absence or presence of CD200 expression in MMCs predicted event-free survival for patients independently of International Staging System (ISS) stage or b-2 microglobulin serum levels. The authors concluded that CD200 is an independent prognostic factor for patients with multiple myeloma that could represent a new therapeutic target in MM.

Moreaux J, Hose D, Reme T, et al. CD200 is a new prognostic factor in multiple myeloma. Blood. 2006;108:4194–4197.

Correspondence: Bernard Klein, INSERM U475, 99, rue Puech Villa, 34197 Montpellier Cedex 5, France; klein@montp.inserm.fr

Cytokeratins 7 and 20 in primary and secondary ovarian mucinous tumors

Among ovarian epithelial tumors, mucinous tumors pose the greatest difficulty with regard to distinguishing primary from metastatic tumors. Primary ovarian mucinous tumors, including the atypical proliferative (borderline) tumors and carcinomas, are usually easily distinguished from metastatic mucinous carcinomas and secondary involvement by appendiceal low-grade adenomatous mucinous tumors in the ovaries when they exhibit characteristic gross and microscopic features. Primary ovarian mucinous tumors are typically large (usually greater than 15 cm), unilateral, multicystic tumors with smooth capsules and are most often not associated with extra-ovarian disease. Primary ovarian mucinous carcinomas most often arise in association with atypical proliferative tumors. Although they can exhibit destructive stromal invasion, they frequently display confluent glandular or expansile, rather than infiltrative, patterns of invasion. In contrast, typical features of secondary mucinous tumors in the ovary that distinguish them from primary tumors include bilaterality, small size (often less than 10 cm), ovarian surface involvement, a nodular pattern of involvement, and an infiltrative pattern of stromal invasion. However, some metastatic mucinous carcinomas can manifest one or more gross and microscopic features, suggesting a primary ovarian tumor clinically and pathologically. Coordinate expression profiles for cytokeratin 7 and 20 (CK7 and CK20) are useful for distinguishing certain types of adenocarcinomas. However, they are of limited usefulness for distinguishing between primary and secondary mucinous tumors in the ovary due to a number of tumor types exhibiting overlapping CK7/CK20 immunoprofiles. The authors conducted a study in which they reported coordinate expression profiles and staining distribution in 179 classified mucinous tumors in the ovary, including 53 primary tumors (35 borderline mucinous tumors of gastrointestinal type and 18 invasive mucinous carcinomas) and 126 secondary tumors (28 colorectal adenocarcinomas, 54 appendiceal tumors [23 adenocarcinomas and 31 low-grade adenomatous mucinous tumors associated with pseudomyxoma peritonei], 14 pancreatic adenocarcinomas, eight endocervical adenocarcinomas, five gastric adenocarcinomas, four gallbladder/biliary tract adenocarcinomas, and 13 adenocarcinomas of unknown primary sites). A CK7+/CK20+ immunoprofile was the most common profile in primary ovarian tumors (74%), upper gastrointestinal tract tumors (78%), and endocervical tumors (88%) but was occasionally observed in lower intestinal tract tumors (colorectal, 11%; appendiceal, 13% of low-grade tumors, 35% of carcinomas). A CK7–/CK20+ immunoprofile was the most common profile in lower intestinal tract tumors (79%), uncommon in upper gastrointestinal tract tumors (9%), rarely seen in primary ovarian tumors (4%), and not seen in endocervical tumors. A CK7+/CK20– profile was observed in some primary ovarian (23%), upper gastrointestinal tract (13%), and endocervical tumors (13%) but not in lower intestinal tract tumors. For CK7+ tumors, staining distribution was very frequently diffuse (more than 50% of tumor cells positive) in primary ovarian, upper gastrointestinal tract, and endocervical tumors, whereas staining distribution was often focal (fewer than 50% of tumor cells positive) in colorectal and appendiceal carcinomas but not in low-grade appendiceal tumors. For CK20+ tumors, staining distribution was variable but often focal in primary ovarian tumors and non-lower intestinal tract tumors, whereas the pattern was almost always diffuse in lower intestinal tract tumors. The authors concluded that immunohistochemical staining distribution can supplement CK7/CK20 coordinate expression profiles to distinguish subsets of primary ovarian and metastatic lower intestinal tract mucinous tumors having overlapping immunoprofiles. But neither coordinate expression profiles nor staining distribution distinguishes primary ovarian tumors from the non-lower intestinal tract metastases.

Vang R, Gown AM, Barry TS, et al. Cytokeratins 7 and 20 in primary and secondary mucinous tumors of the ovary: analysis of coordinate immunohistochemical expression profiles and staining distribution in 179 cases. Am J Surg Pathol. 2006;30:1130–1139.

Reprints: Dr. Russell Vang, Johns Hopkins Hospital, Division of Gynecologic Pathology, Weinberg Building, Room 2242, 401 N. Broadway, Baltimore, MD 21231; rvang1@jhmi.edu

Prognostic role of a gene signature from tumorigenic breast cancer cells

Breast cancers contain a minority population of cancer cells characterized by CD44 expression but low or undetectable levels of CD24 (CD44+CD24–/low) that have higher tumorigenic capacity than other subtypes of cancer cells. The authors compared the gene-expression profile of CD44+CD24–/low tumorigenic breast cancer cells with that of normal breast epithelium. Differentially expressed genes were used to generate a 186-gene invasiveness gene signature (IGS), which was evaluated for its association with overall survival and metastasis-free survival in patients with breast cancer or other types of cancer. The authors found a significant association between the IGS and overall and metastasis-free survival (P<0.001, for both) in patients with breast cancer, which was independent of established clinical and pathological variables. When combined with the prognostic criteria of the National Institutes of Health, the IGS was used to stratify patients with high-risk early breast cancer into prognostic categories (good or poor). Among patients with a good prognosis, the 10-year rate of metastasis-free survival was 81 percent; among those with a poor prognosis, it was 57 percent. The IGS was also associated with prognosis in medulloblastoma (P=0.004), lung cancer (P=0.03), and prostate cancer (P=0.01). The prognostic power of the IGS was increased when combined with the wound-response signature. The authors concluded that the IGS is strongly associated with metastasis-free survival and overall survival for four types of tumors. This genetic signature of tumorigenic breast cancer cells was even more strongly associated with clinical outcome when combined with the wound-response signature in breast cancer.

Liu R, Wang X, Chen GY, et al. The prognostic role of a gene signature from tumorigenic breast-cancer cells. N Engl J Med. 2007;356:217–226.

Reprint information not available.