ABSTRACT
PURPOSE: CD44 is a cell surface receptor implicated in cancer progression and metastases. Malignant tumors may show a loss of CD44 splice control mechanisms. We investigated the role of CD44 splice variant expression in ovarian tumors and metastases, and its association with survival. EXPERIMENTAL DESIGN: We tested CD44 expression in 142 cases of epithelial carcinoma of the ovary and 265 metastatic sites by immunohistochemistry. RESULTS: Survival analysis showed that the expression of CD44s, CD44-v4, -v5, -v6, -v9, and -v10 are significant predictors for survival in univariate analysis. After stage, the expression of CD44-v10 in metastases was the strongest predictor of decreased survival in multivariate analysis (p = 0.0009). Conversely, CD44-v10 expression in the primary tumor was an independent predictor of improved survival in multivariate analysis (p = 0.0002). The expression of CD44s in the tumor/stroma interface of the primary tumor was associated with improved survival (p < 0.0001). CONCLUSIONS: CD44 variant expression is a molecular prognostic maker for epithelial ovarian carcinomas. CD44-v10 expression is an independent prognostic indicator and the site of expression determines a positive or negative influence in survival. Our results also indicate that CD44 may be involved in important tumor/stroma interactions.
Subject(s)
Biomarkers, Tumor/metabolism , Hyaluronan Receptors/metabolism , Neoplasm Proteins/metabolism , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/mortality , Adenocarcinoma, Mucinous/metabolism , Adenocarcinoma, Mucinous/mortality , Adenocarcinoma, Mucinous/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Endometrioid/metabolism , Carcinoma, Endometrioid/mortality , Carcinoma, Endometrioid/pathology , Cystadenocarcinoma, Serous/metabolism , Cystadenocarcinoma, Serous/mortality , Cystadenocarcinoma, Serous/pathology , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Staging , Ovarian Neoplasms/pathology , Prognosis , Survival RateABSTRACT
BACKGROUND: Prostate cancer metastases to bone are associated with significant morbidity and mortality. Presently, there is little known about the biological interaction between prostate cancer cells and bone. Development of an animal model using adult human bone will enhance our ability to study the biology of prostate cancer metastasis to bone. METHODS: Bone was harvested from patients undergoing total joint arthroplasty and implanted in the hindlimbs of pre-treated SCID mice. Two months after bone implantation 4 x 104 prostate cancer cells (PC-3 or LAPC-4) were injected near the bone implantation site. The animals were sacrificed approximately 8 to 12 weeks after the injections of the cells. Complete histological analysis including immunostaining was performed. RESULTS: Both the PC-3 and LAPC-4 prostate cancer cells homed to the human bone implant, specifically the reconstituted bone marrow cavity. Analysis of the bone-tumor interaction after injection of PC-3 cells revealed strong labeling for PTHrP, TNF alpha and IL-6, consistent with osteoclast recruitment and osteoclast activity. These cells also were positively stained for CK18. After cellular injection of LAPC-4 cells, there was strong labeling for TNF alpha, IL-6, and IL-1 (osteoclast recruitment and osteolytic activity). PTHrP staining was also noted. The bone cells were strongly stained for osteocalcin, and the tumor cells for PSA. CONCLUSIONS: These data suggest that the tumor cells may induce an osteolytic response to enhance their ability to metastasize to bone. This animal model allows us to study the biologic interaction between prostate cancer cells and human bone and may enhance our understanding of the events associated with prostate cancer metastasis to bone.
Subject(s)
Adenocarcinoma/pathology , Bone Neoplasms/secondary , Disease Models, Animal , Prostatic Neoplasms/pathology , Adenocarcinoma/metabolism , Animals , Bone Development , Bone Neoplasms/metabolism , Humans , Male , Mice , Mice, SCID , Prostatic Neoplasms/metabolismABSTRACT
Intraductal papillary-mucinous tumors of the pancreas are increasingly recognized, and their characteristic endoscopic and radiological features are well reported in the literature in recent years. Oncocytic features in these tumors are uncommon and unrecognized. Intraductal oncocytic papillary neoplasm is a distinct pancreatic tumor and is a recently recognized entity. We report a case of a 69-yr-old patient who presented with symptoms mimicking pancreatitis, resulting in delay in the diagnosis of her pancreatic tumor. She underwent a successful Whipple's procedure and subsequently has remained well. The resected specimen showed an intraductal oncocytic papillary-mucinous neoplasm. The entity is new and the literature information is inadequate at present to judge the biological behavior of this tumor. We discuss this recently recognized entity.
Subject(s)
Pancreatic Ducts/pathology , Pancreatic Neoplasms/pathology , Aged , Cholangiopancreatography, Endoscopic Retrograde , Cysts/pathology , Female , Humans , Pancreatic Ducts/diagnostic imaging , Pancreatic Neoplasms/diagnostic imaging , Tomography, X-Ray ComputedABSTRACT
A 32-year-old, previously healthy woman with a diffuse, complex tumoral process is described. While she was being evaluated for primary infertility, a laparoscopic procedure revealed a disseminated peritoneal process associated with bilateral ovarian lesions. A clinical diagnosis of stage III ovarian cancer was made and total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy were performed. Pathologic studies showed an admixture of leiomyomatosis peritonealis disseminata (LPD) endometriosis, and an extensive multicystic mesothelial proliferation. Although endometriosis is known to occur in conjunction with either LPD or multicystic mesothelioma, to our knowledge this is the first report of all three lesions occurring simultaneously.
