Extraskeletal osteosarcoma in Norway, between 1975 and 2009, and a brief review of the literature.

AIM: To evaluate the clinicopathological features of extraskeletal osteosarcoma (ESOS) and its response to multimodal therapy. PATIENTS AND METHODS: A nationwide cohort comprising all Norwegian histologically verified ESOS patients between 1975 and 2009 supplemented with clinical reports from all hospitals involved in sarcoma management. RESULTS: Thirty-seven patients were classified as ESOS, mostly elderly people. Seventy-six % had an axial tumour, including nine patients with radiation-induced ESOS. The gender balance was equal. The 5-year sarcoma-specific survival (SSS) was 16 %. Adequate surgical remission had a positive impact on SSS, in contrast to chemotherapy and radiotherapy. Primary metastatic disease, elevated tumour size and elevated serum alkaline phosphatase, serum lactate dehydrogenase and Ki67, respectively, all predicted poor outcome. CONCLUSION: The relatively poor prognosis of ESOS may relate to both primary chemotherapy resistance and different biologic characteristics of these tumours as compared to conventional osteosarcoma. Hence, new predictive molecular markers and therapeutic approaches for treatment of ESOS are needed.

Time-trends on incidence and survival in a nationwide and unselected cohort of patients with skeletal osteosarcoma.

BACKGROUND: This study describes time-trends on epidemiology, subtypes and histopathological entities of osteosarcoma (OS) in a nationwide and unselected cohort of OS patients in Norway between 1975 and 2009. Few nationwide studies are published, and we still have particularly limited knowledge regarding patients not included in clinical trials comprising about half of the OS population. METHOD: Histologically verified skeletal OS for all subgroups were included, resulting in 473 eligible cases from a total of 702 evaluated patients. To ensure completeness, the present cohort was based on all cases reported to the Norwegian Cancer Registry, complemented with data from all Norwegian hospitals involved in sarcoma management. Survival analyses were performed with overall and sarcoma-specific survival as endpoints. RESULTS: Mean annual age-standard incidence amounted to about 3.8 per million in male and 2.8 per million in female with no clear time-trends. The male to female ratio was 1.4. Peak incidence was observed in the second decade for both genders. Conventional OS comprised 71.2% of all cases, while low grade OS represented 10.4% and telangiectatic OS only 1.3%. The most common primary site of OS was femur and tibia, respectively. The axial to appendicular ratio increased with the age. The overall 10-year survival did increase from about 30% during the late 1970s to around 50% 20 years later, with no subsequent improvement during the last two decades. Axial tumours, age above 40 years and overt metastatic disease at time of diagnosis were all negative prognostic factors. CONCLUSION: No improvement in the overall survival for OS since the 1990s was documented. The survival rates are still poor for elderly people, patients with axial disease and in the primary metastatic setting. The average incidence rate of skeletal OS in Norway was in line with international figures.

Stem cell marker-positive stellate cells and mast cells are reduced in benign-appearing bladder tissue in patients with urothelial carcinoma.

Survival after invasive bladder cancer has improved less than that of other common non-skin cancers. In many types of malignancy, treatment failure has been attributed to therapy-resistant stem-like cancer cells. Our aim was therefore to determine identities of stem cell marker-positive cells in bladder cancer tissue and to investigate possible associations between these cells and different forms of bladder neoplasia. We investigated tissue from 52 patients with bladder neoplasia and 18 patients with benign bladder conditions, from a cohort that had been previously described with regard to diagnosis and outcome. The samples were analysed immunohistologically for the stem cell markers aldehyde dehydrogenase 1 A1 (ALDH1) and CD44, and markers of cell differentiation. The majority of stem cell marker-positive cells were located in connective tissue, and a smaller fraction in epithelial tissue. Stem cell marker-positive cells exhibiting possible stem cell characteristics included cells in deeper locations of benign and malignant epithelium, and sub-endothelial cells in patients with or without neoplasia. Stem cell marker-positive cells with non-stem cell character included stellate cells, mast cells, endothelial cells, foamy histiocytes, and neurons. Significantly, ALDH1+ stellate cells and ALDH1+ mast cells were reduced in number in stroma of benign-appearing mucosa of bladder cancer patients. The stem cell markers ALDH1 and CD44 label several types of differentiated cells in bladder tissue. ALDH1+ stellate cells and mast cells appear to be reduced in stroma of normal-appearing mucosa of bladder cancer patients, and may be part of a "field effect" in cancer-near areas.

Survey of 548 oncogenic fusion transcripts in thyroid tumors supports the importance of the already established thyroid fusions genes.

Neoplasms frequently present structural chromosomal aberrations that can alter the level of expression of a protein or to the expression of an aberrant chimeric protein. In the thyroid, the PAX8-PPARG fusion is present in the neoplastic lesions that have a follicular architecture-follicular thyroid carcinoma (FTC) and follicular variant of papillary thyroid carcinoma (FVPTC), and less frequently in follicular thyroid adenoma (FTA), while the presence of RET/PTC fusions are largely restricted to papillary thyroid carcinoma (PTC). The ability to detect fusion genes is relevant for a correct diagnosis and for therapy. We have developed a new fusion gene microarray-based approach for simultaneous analysis of all known and predicted fusion gene variants. We did a comprehensive screen for 548 known and putative fusion genes in 27 samples of thyroid tumors and three positive controls-one thyroid cancer cell line (TPC-1) and two PTCs with known CCDC6-RET (alias RET/PTC1) fusion gene, using this microarray. Within the thyroid tumors tested, only well known, previously reported fusion genes in thyroid oncology were identified. Our results reinforce the pathogenic role played by RET/PTC1, RET/PTC3, and PAX8-PPARG fusion genes in thyroid tumorigenesis.

The diagnostic and research applications of flow cytometry in cytopathology.

Flow cytometry (FCM) is an established ancillary technique applied to the diagnosis of hematological malignancies and for measurement of DNA content. In recent years, the number of fluorochrome-conjugated antibodies available for immunofluorescence and FCM has greatly increased, making it possible to evaluate this technique in other diagnostic contexts, as well as to study a range of biological processes. Serous effusions are optimal for studies using FCM as they consist of viable cells in suspension. Molecules that have been studied for their expression and clinical role in effusions in recent years participate in central cellular functions, including adhesion, proliferation, cellular metabolism, and apoptosis, as well as intracellular signaling. FCM can further be applied to quantitative analysis of molecules related to chemotherapy response, which, together with apoptosis, may represent an important tool for evaluating treatment response and prognosis in advanced and/or recurrent cancer. As targeted therapy assumes an ever-growing role in the treatment of metastatic cancer, the ability to study living cells in effusions or fine-needle aspirates is becoming more important. This article reviews the currently available data in this area of cytopathology.

The new molecular markers DDIT3, STT3A, ARG2 and FAM129A are not useful in diagnosing thyroid follicular tumors.

Preoperative characterization of thyroid follicular lesions is challenging. Fine-needle aspiration specimens cannot differentiate follicular carcinomas from benign follicular neoplasias. Recently, promising markers have been detected using modern molecular techniques. We conducted a retrospective study to confirm the usefulness of immunohistochemical staining for the protein markers, DDIT3, STT3A (ITM1), ARG2 and FAM129A (C1orf24) in separating benign and malignant thyroid follicular lesions. Formalin-fixed, paraffin-embedded thyroid tissue from 30 in-house cases (15 follicular carcinomas and 15 follicular adenomas), as well as 8 follicular carcinomas and 21 follicular adenomas on tissue microarray slides were stained immunohistochemically for DDIT3, STT3A, ARG2 and FAM129A expression. Control tissue consisted of thyroid parenchyma adjacent to the tumors and 11 separate cases of normal thyroid parenchyma. All in-house cases of follicular adenomas, follicular carcinomas and adjacent normal thyroid tissue showed positive immunostaining with anti-DDIT3 and anti-STT3A. Anti-ARG2 and anti-FAM129A polyclonal antibodies showed positive staining in 20 and 60% of in-house follicular adenomas, and 40 and 87% of in-house follicular carcinomas, respectively. Monoclonal anti-FAM129A demonstrated positive staining in 13 and 33% of in-house follicular adenomas and follicular carcinomas, respectively. Polyclonal anti-DDIT3, -STT3A and -FAM129A antibodies showed positive staining in all tissue microarray slides of follicular carcinoma and in 76, 85 and 81% of the follicular adenomas, respectively. Monoclonal anti-STT3A stained 81% of the follicular adenoma cores. Anti-ARG2 stained positive in 13% of follicular carcinomas and 10% of follicular adenomas on the tissue microarray slides. In conclusion, DDIT3, STT3A, ARG2 and FAM129A immunohistochemistry does not appear to be useful in the diagnosis of thyroid follicular neoplasias, as they do not reliably distinguish follicular thyroid carcinoma from follicular thyroid adenoma.

Efficacy of ultrasound-guided percutaneous ethanol injection treatment in patients with a limited number of metastatic cervical lymph nodes from papillary thyroid carcinoma.

CONTEXT: Repeated neck explorations can be a difficult task in patients with recurrent metastatic cervical lymph nodes from papillary thyroid carcinoma (PTC). OBJECTIVE: The aim of this retrospective study has been to assess the efficacy of ultrasound (US)-guided percutaneous ethanol injection (PEI) as treatment of metastatic cervical lymph nodes from PTC. MATERIALS AND METHODS: Sixty-nine patients who previously had undergone thyroidectomy for PTC were selected for inclusion. However, three patients were later excluded due to lack of follow-up. Lymph node status was determined by US-guided fine-needle aspiration biopsy and/or by raised levels of thyroglobulin in washouts from the cytological needle. Guided by US, 0.1-1.0 ml of 99.5% ethanol was injected into the metastatic lymph nodes. RESULTS: Three patients (eight metastatic lymph nodes in total) were reassigned to surgery due to progression (multiple new metastases), leaving 63 patients and 109 neck lymph nodes to be included. Mean observation time was 38.4 months (range, 3-72). A total of 101 of the 109 (93%) metastatic lymph nodes responded to PEI treatment, 92 (84%) completely and nine incompletely. Two did not respond, and four progressed. Two lymph nodes previously considered successfully treated showed evidence of malignancy during follow-up. No significant side effects were reported. CONCLUSION: US-guided PEI treatment of metastatic lymph nodes seems to be an excellent alternative to surgery in patients with a limited number of neck metastases from PTC. This procedure should replace "berry picking" surgery.

Metastatic malignant melanoma mimicking benign breast cysts.

Benign cysts are one of the most common mass-occupying lesions of the breast and are often investigated with triple diagnostic trial (clinical examination, radiology, and cytology). Malignant melanoma is one of medicine's imitators, and metastatic disease can mimic cysts. Thorough investigation of any breast mass is essential to clarify its nature.

Fine-needle aspiration cytology of the breast.

Fine-needle aspiration cytology (FNAC) is an established, highly accurate, and cost-effective method for diagnosing lesions in different organs, including the breast. The method is minimally invasive without unwanted side effects. FNAC forms part of the triple assessment of breast lesions. Despite some shortcomings of the reporting categories, FNAC as part of the triple assessment has proved its value in describing the findings most accurately. The diagnostic impact depends on experience of the operator, quality of preparation, and diagnostic skills of the cytopathologist. The highest accuracy is achieved at centers with a multidisciplinary approach. FNAC is often palpation guided from palpable breast masses, whereas ultrasonography guidance is more widely used on nonpalpable lesions. Inadequate sampling with FNAC is particularly seen in collagenous lesions and in submitted specimens sampled by physicians lacking experience with the FNAC procedure. A diagnostic biopsy is recommended when FNAC provides scant material. FNAC is considered to be a safe method for screening purposes, although moderately less sensitive than core needle biopsy. FNAC is most accurate when experienced cytopathologists are available to assess the adequacy of the aspirated material and advise on additional aspirations for ancillary tests when needed.

Endoglin (CD105) expression in ovarian serous carcinoma effusions is related to chemotherapy status.

Endoglin (CD105), a cell surface co-receptor for transforming growth factor-ß, is expressed in proliferating endothelial cells, as well as in cancer cells. We studied endoglin expression and its clinical relevance in effusions, primary tumors, and solid metastatic lesions from women with advanced-stage ovarian serous carcinoma. Endoglin expression was analyzed by immunohistochemistry in effusions (n = 211; 174 peritoneal, 37 pleural). Cellular endoglin staining was analyzed for association with the concentration of soluble endoglin (previously determined by ELISA) in 95 corresponding effusions and analyzed for correlation with clinicopathologic parameters, including survival. Endoglin expression was additionally studied in 34 patient-matched primary tumors and solid metastases. Carcinoma and mesothelial cells expressed endoglin in 95/211 (45%) and 133/211 (63%) effusions, respectively. Carcinoma cell endoglin expression was more frequent in effusions from patients aged ≤ 60 years (p = 0.048) and in post- compared to prechemotherapy effusions (p = 0.014), whereas mesothelial cell endoglin expression was higher in prechemotherapy effusions (p = 0.021). No association was found between cellular endoglin expression and its soluble effusion concentration. Endoglin was expressed in 17/34 (50%) primary tumors and 19/34 (56%) metastases, with significantly higher percentage of immunostained cells in solid metastases compared to effusions (p = 0.036). Endoglin expression did not correlate with survival. Tumor cell endoglin expression is higher in post- vs. prechemotherapy effusions, whereas the opposite is seen in mesothelial cells. Together with its upregulation in solid metastases, this suggests that the expression and biological role of endoglin may differ between cell populations and change along tumor progression in ovarian carcinoma.

CD105 (Endoglin) expression in breast carcinoma effusions is a marker of poor survival.

We analyzed the expression and clinical role of endoglin (CD105) in breast carcinoma effusions. Endoglin levels were measured in 36 effusion supernatants by ELISA and studied for association with the cancer-associated markers calprotectin, VEGF, and the VEGF receptor sFlt1. Endoglin expression was further studied in 46 effusions and 22 primary carcinomas using immunohistochemistry. The four secreted molecules were detected in all specimens and their levels significantly correlated (p < 0.001). In effusions, endoglin was localized to carcinoma cells and reactive mesothelium using immunohistochemistry. Tumor cell expression was higher in effusions compared to primary carcinomas (p = 0.025), and in post-chemotherapy compared to pre-chemotherapy effusions (p = 0.017). Higher tumor endoglin expression was associated with poor overall (p = 0.021) and disease-free (p = 0.032) survival in univariate analysis, and was an independent predictor in Cox multivariate analysis (p = 0.001 and p = 0.038, respectively). Our data suggest that endoglin may be an important therapeutic target in metastatic breast cancer.

Nuclear factor kappaB transcription factors are coexpressed and convey a poor outcome in ovarian cancer.

BACKGROUND: Recent work has suggested a role for nuclear factor kappaB (NF-kappaB) in the propagation of ovarian cancer cell lines, but the significance and mechanism of NF-kappaB in ovarian cancer is unknown. The authors hypothesized that the NF-kappaB pathway is over activated in aggressive ovarian cancers. METHODS: The levels of 3 NF-kappaB transcription factors, the activating inhibitors of NF-kappaB (IkappaB) kinases, and the NF-kappaB target matrix metalloproteinase 9 (MMP9) were assessed by immunohistochemistry in specimens of ovarian cancer that were obtained at diagnosis from a cohort of 33 patients who subsequently received combined paclitaxel, cisplatin, and cyclophosphamide. Associations were made between NF-kappaB pathway proteins and outcome. The validation of coexpression was performed at the gene level in 2 independently collected cohorts of 185 and 153 ovarian cancers. RESULTS: The presence of NF-kappaB proteins in newly diagnosed advanced ovarian cancers was established, and a potential association with overall survival was identified. Transcription factors p65 and v-rel reticuloendotheliosis viral oncogene homolog B (RelB) were coexpressed with IkappaB kinase alpha, 1 component of a key trimolecular regulatory complex. Coexpression of the NF-kappaB machinery suggested activity of NF-kappaB signaling in these ovarian tumors. A significant association of p50 with poor overall survival was observed (P = .02). MMP9 expression had the opposite association, in which patients who had tumors without MMP9 staining had the poorest prognosis (P = .01), and this association held true at the gene expression level in an independently collected cohort of 185 ovarian cancers. CONCLUSIONS: The deregulation of NF-kappaB activity may influence outcome in women who receive standard therapy for advanced ovarian cancer. Modification of the NF-kappaB pathway may present an opportunity to improve outcome in the subset of women who have pathway activity.

Expression and clinical role of growth differentiation factor-15 in ovarian carcinoma effusions.

INTRODUCTION: Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor-ß family. We analyzed the expression and clinical role of GDF-15 in ovarian carcinoma effusions. METHODS: The concentration of soluble GDF-15 was measured in 195 effusion supernatants from 162 patients with ovarian carcinoma by an immunoradiometric assay. Tumor cell GDF-15 expression was investigated in 114 effusions from the same patients using immunohistochemistry. RESULTS: Growth differentiation factor-15 was detected in all effusion supernatants by immunoradiometric assay. Growth differentiation factor-15 cytoplasmic expression in carcinoma cells was seen in 111 (97%) of 114 specimens. Effusion GDF-15 concentration correlated positively with GDF-15 tumor cell expression (P < 0.001). Growth differentiation factor-15 concentration was higher in effusions from patients who previously received chemotherapy compared with specimens from patients not treated with chemotherapy (P = 0.028). High GDF-15 effusion concentration was associated with poor response to chemotherapy at first disease recurrence (P = 0.001). In univariate survival analysis, high concentration of GDF-15 in effusions was associated with poor overall survival (P = 0.016), and this finding retained its prognostic value in Cox multivariate analysis (P = 0.01). Tumor cell expression of GDF-15 did not correlate with survival in analysis of the entire cohort. However, high tumor cell GDF-15 expression in prechemotherapy specimens was associated with poor progression-free survival (P = 0.046). CONCLUSIONS: Soluble GDF-15 is universally present in effusions from patients with ovarian carcinoma, and tumor cells represent a likely source for soluble GDF-15 in effusions. Growth differentiation factor-15 emerges as a potential prognostic biomarker in ovarian carcinoma.

Concordance between Gleason scores of needle biopsies and radical prostatectomy specimens: a population-based study.

OBJECTIVE: To study the concordance between the Gleason scores of needle biopsies and radical prostatectomy (RP) specimens in a population-based registry, to clarify whether the concordance depends on the annual number of RP specimens assessed in the pathology unit, and to identify preoperative clinical factors that predict upgrading from a Gleason score of or=7 in the RP specimen. PATIENTS AND METHODS: Through the Cancer Registry of Norway, we identified 1116 patients with available Gleason scores from biopsy and RP specimens. Concordance was evaluated using the kappa coefficient, and predictors of concordance were assessed in univariate and multivariate logistic regression analyses. RESULTS: The Gleason scores were identical in biopsy and RP specimens in 591 of the 1116 (53%) patients. The biopsy-based Gleason score more often under-graded (38%) than over-graded (9%) the RP-based Gleason score. Pathology units that examined >40 RP specimens annually had a higher concordance between the Gleason score in the biopsy and RP specimen than did lower-volume units. The rate of upgrading from a Gleason score of or=7 in the RP specimen increased with increasing preoperative prostate-specific antigen serum levels, and with increasing intervals between biopsy and RP. CONCLUSIONS: The concordance in Gleason score between biopsy and RP was highest among the pathology departments that regularly evaluated RP specimens. Careful consideration of clinical factors and biopsy grading might improve the identification of patients considered as suitable for active surveillance.

The chemokine receptor CXCR4 is more frequently expressed in breast compared to other metastatic adenocarcinomas in effusions.

This objective of this study was to investigate the expression of chemokine receptors in tumor cells and leukocytes in breast carcinoma effusions. The expression of leukocyte markers (CD3/4/8/14/16/19) and chemokine receptors (CXCR1/4, CCR2/5/7) was studied in 21 breast carcinoma effusions using flow cytometry. Breast carcinoma cells expressed CXCR4 in 7/21 (33%) effusions, with less frequent expression of CXCR1, CCR5, and CCR7. CXCR2 and CCR2 were absent. Lymphocytes showed frequent CXCR4, CCR5, and CCR7 expression, while CXCR1, CXCR2, CCR2 were rarely or never detected. Macrophages expressed all six receptors except for CXCR2. Comparative analysis of breast carcinoma effusions with previously studied ovarian and cervical/endometrial adenocarcinomas (ACs) showed significantly higher CXCR4 expression in breast carcinoma cells compared to the other gynecological ACs (p = 0.001). Breast and cervical/endometrial carcinoma effusions showed different expression of chemokine receptors in lymphocytes (lower CXCR1, higher CXCR4 and CCR7 levels; p = 0.012, p = 0.005, p < 0.001, respectively) and macrophages (higher CCR7 levels; p < 0.001), as well as lower CD8 counts (p < 0.001) and higher CD19 counts (p = 0.001) compared to ovarian carcinoma effusions. Higher numbers of CD8-positive lymphocytes (p = 0.080) and higher CCR7 monocyte expression (p = 0.087) were associated with a trend for shorter disease-free survival. In conclusion, breast carcinoma cells express CXCR4, a unique feature among metastatic ACs in effusions, with rare expression of other chemokine receptors. Chemokine receptor expression in leukocytes and lymphocyte counts significantly differ from those of ovarian carcinoma effusions. The prognostic role of CCR7 expression in monocytes and CD8 counts in breast carcinoma effusions merits further research.

Disseminated tumor cells in bone marrow following definitive radiotherapy for intermediate or high-risk prostate cancer.

BACKGROUND: The purpose of this study was to explore the prevalence of disseminated tumor cells (DTCs) in bone marrow (BM) of clinically progression-free prostate cancer (PC) patients at least 2 years after curatively intended radiotherapy (RT) with or without adjuvant hormone treatment. METHODS: All patients were T(1-3)N(0)M(0) with intermediate or high risk of progression. Median time from RT to BM sampling was 5 years (2-8). A standardized immunocytochemical method applying the anticytokeratin antibodies AE1/AE3 was used for DTCs detection in 130 patients. Morphological characterization of immunostained cells was performed to exclude false positive cells. The post-treatment BM was explored in relation to pre-treatment risk factors, treatment strategy and serum levels of Testosterone and PSA at the time of BM sampling. Longitudinal changes in BM status were studied in a sub-group of 109 patients who also had donated BM prior to treatment. RESULTS: Post-treatment BM-aspirates were positive for DTCs in 17% of cases without correlation to any of the tested variables. Out of 14 patients who had DTCs in BM prior to treatment, all but one had become post-treatment negative. Out of 95 patients with pre-treatment negative BM status, 18 (19%) had become post-treatment positive. CONCLUSIONS: DTCs in BM were found in 17% of clinically progression-free PC patients following RT. The detection of these cells may provide PSA-independent prognostic information remaining to be explored by prolonged follow-up.

S100B in bone marrow aspirates in healthy individuals and malignant melanoma patients.

The aim of this study was to evaluate S100B in bone marrow (BM) plasma from malignant melanoma patients. BM aspirates and peripheral blood (PB) plasma from 56 patients and BM aspirates from 29 healthy volunteers were collected. S100B was measured using an immune radiometric assay, which is a two-site sandwich assay based on monoclonal antibodies recognizing the beta-subunit. In the control population, the median S100B level in BM plasma was 9.0 microg/l (26 women and three men), an unexpectedly high value compared with the median S100B level in PB<0.05 microg/l. S100B levels in BM seems to be sex dependent. Median S100B levels in samples taken from male melanoma patients was 26.7 microg/l in contrast to 9.3 microg/l in female patients (Mann-Whitney P<0.002). The elevated BM S100B in melanoma patients could not be explained by presence of melanoma cells in the BM, as the values also were increased to the same extent in patients with no detectable BM metastases. In attempts to identify the source of S100B in BM, cytospins from five patients with high S100B values were stained, but none of the BM cells stained positive. S100B levels in PB were dependent on the stage of melanoma disease and there was a significant shorter survival time in the group of patients with elevated S100B compared with the group with normal S100B values, (log rank test: P=0.04). In BM taken from melanoma patients, however, there were no association between S100B levels and survival. The median S100B level in BM aspirates from healthy female volunteers and BM samples from female melanoma patients were 8.1 and 9.3 microg/l both manifold higher than the cut-off value for S100B in PB (0.2 microg/l). The median S100B in the samples taken from male melanoma patients was nearly three times higher than in the female patients. Unlike S100B in PB, S100B in BM demonstrated no prognostic value. The explanation for the unexpected high S100B in BM remains elusive.

Expression of the chromatin remodeling factor Rsf-1 is down-regulated in breast carcinoma effusions.

We recently identified Rsf-1, a chromatin-remodeling gene, as a potential oncogene that is frequently amplified and overexpressed in ovarian serous carcinoma, and demonstrated that its expression in carcinoma cells in effusions is associated with poor prognosis. In the present study, we assessed the clinical significance of Rsf-1 overexpression in breast carcinoma effusions. Formalin-fixed paraffin-embedded sections from 47 effusions were analyzed for Rsf-1 expression by immunohistochemistry. Matched primary tumors (n = 30) and solid metastases (n = 26) from 30 patients were additionally studied. Rsf-1 expression in tumor cells in effusions was analyzed for association with clinicopathologic parameters and survival. Rsf-1 protein expression was found in carcinoma cells in 34 (72%) of 47 effusions, 24 (80%) of 30 primary carcinomas, and 24 (92%) of 26 metastases. Rsf-1 immunoreactivity in effusions showed no association with HER-2 or hormone receptor status. Rsf-1 expression level was significantly lower in effusions compared with primary tumors (P = .026 and P = .011 for extent and intensity, respectively) and lymph node metastases (P = .023 and P = .013 for extent and intensity, respectively). Staining extent and intensity were both significantly lower in breast compared with ovarian carcinoma effusions (P = .001 for extent, P < .001 for intensity). Rsf-1 expression showed no association with survival. In conclusion, in contrast to ovarian carcinoma, Rsf-1 expression is down-regulated in breast carcinoma cells in effusions compared with the solid counterparts and has no prognostic role at this anatomic site.