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Ben Davidson

Publications and source records attributed to Ben Davidson.

At least 37 records · Page 2Linked to original sources
PubMed2006

The p75 neurotrophin receptor is widely expressed in conventional papillary thyroid carcinoma.

Papillary thyroid carcinomas (PTCs) are associated with alterations in several proto-oncogenes related with nervous system development and function, such as TrkA and RET, which are commonly rearranged in these carcinomas. The other oncogenic event recently identified in PTC is the BRAF V600E mutation. Because the role of TrkA was not completely elucidated in thyroid cancer ethiopathogenesis, we decided to study the expression of active, phosphorylated TrkA and of its coreceptor p75 neurotrophin receptor (p75 NTR) in a series of 92 PTC (37 lesions of conventional PTC, 28 of follicular variant of PTC [FVPTC], and 27 of other variants of PTC) as well as in 21 samples of normal thyroid and nonneoplastic thyroid lesions used as a controls. We observed neoexpression of p75 NTR in PTC, particularly in conventional PTC and in other variants of PTC displaying a papillary growth pattern, rather than in FVPTC. No immunoexpression of p75 NTR was observed in normal thyroid nor in nonneoplastic thyroid lesions. The cellular localization of p75 NTR immunoexpression was also significantly associated with the growth pattern of PTC, being much more frequently detected in an apical localization in PTC with papillary architecture than in PTC with a follicular or solid growth pattern. This apical localization of p75 NTR was significantly associated with the presence of BRAF V600E. No significant differences were detected between normal thyroid, nonneoplastic lesions, and PTC (or any PTC variant) regarding expression/activation of TrkA, thus suggesting that by itself and in contrast to p75 NTR, TrkA is not altered during PTC development.

Adenocarcinoma, Papillary↗
PubMed2006

The biological differences between ovarian serous carcinoma and diffuse peritoneal malignant mesothelioma.

Recent improvements in immunohistochemistry panels used for differentiating ovarian serous carcinoma/primary peritoneal carcinoma (OC/PPC) from diffuse malignant peritoneal mesothelioma (DMPM) have resulted in improved diagnostic rates for these tumors in both cytological and histological material. However, little is known about the biological characteristics that differentiate these two cancer types. We performed a comparative analysis of cancer-associated molecule expression data for a cohort consisting of up to 270 serous OC/PPC specimens (only peritoneal lesions) and 32 peritoneal MM. The molecules studied were nerve growth factor receptors (p75, p-TrkA), angiogenic factors (VEGF, IL-8, bFGF, heparanase), laminin receptors (the 67-kDa receptor and the alpha 6 integrin subunit), proteases (MMP-2), immune response mediators (HLA-G), and signaling molecules (the MAPK members ERK, JNK, and p38). The methods used were immunohistochemistry, Western blotting, and RT-PCR. DMPM specimens showed significantly higher expression of p75 (P < 0.001), p-TrkA (P < 0.001), and bFGF (P < 0.001), and significantly lower expression of the 67-kDa receptor (P < 0.001), alpha 6 integrin subunit (P = 0.025), VEGF (P < 0.001), IL-8 (P < 0.001), and HLA-G (P = 0.039) compared with OC/PPC. DMPM specimens showed higher activation ratio (phosphorylated/total enzyme ratio) of all three MAPK members (ERK, P = 0.017; JNK, P < 0.001; p38, P = 0.009) compared with OC/PPC. These data document significant differences in the expression of cancer- and metastasis-associated molecules in MM compared with ovarian carcinoma, and suggest that different biological pathways are involved in tumorigenesis and disease progression in these two tumors.

Biomarkers, Tumor↗
PubMed2006

D2-40 is not a specific marker for cells of mesothelial origin in serous effusions.

The presence of effusion in a patient with a history of primary malignant tumor elsewhere in the body is generally accepted as a clinical manifestation of metastatic disease. Even in those cases, it is sometimes difficult to differentiate reactive mesothelial cells from carcinoma cells. Another challenging issue especially in the field of serous effusions is the differential diagnosis between malignant mesothelioma and metastatic adenocarcinoma. The aim of this study was to evaluate the potential use of the D2-40 antibody detecting the M2A oncofetal antigen in the diagnosis of malignant serous effusions. Two hundred and ninety effusion specimens (169 ovarian carcinomas, 44 breast carcinomas, 32 malignant mesotheliomas, 6 lung carcinomas, 8 reactive specimens, and 31 tumors of other origin) were assessed. Expression in reactive mesothelial cells was additionally assessed on 145 malignant effusions. Immunohistochemical analysis using the EnVision system was performed. M2A antigen was expressed in malignant mesotheliomas and reactive mesothelial cells in all specimens. Positive membranous staining was observed in 58% of ovarian carcinomas, 33% of lung carcinomas, and 30% of breast carcinomas. Pulmonary, breast, and nonovarian gynecologic tumors usually showed weak focal membranous staining, whereas the ovarian adenocarcinomas showed an expression pattern more similar to mesotheliomas. The results from the present study suggest low specificity for D2-40 as a mesothelial marker, especially in the context of differentiating mesothelial cells from ovarian carcinoma, and argue against its inclusion in the diagnostic panel of serous effusions.

Adenocarcinoma↗
PubMed2006

NK- and B-cell infiltration correlates with worse outcome in metastatic ovarian carcinoma.

We studied the clinical role of leukocyte infiltration and chemokine receptor expression in ovarian carcinoma effusions. Expression of leukocyte markers (CD3, CD4, CD8, CD4/CD8 ratio, CD16, CD19, and CD14) and chemokine receptors (CXCR1, CXCR4, CCR2, CCR5, and CCR7) was studied in 73 effusions by using flow cytometry. CXCR4, CCR5, and CCR7 were expressed abundantly on leukocytes, but all receptors were expressed rarely on cancer cells. The presence of natural killer cells (P = .042) and International Federation of Gynecology and Obstetrics (FIGO) stage IV disease (P = .024) predicted worse overall survival (OS). A higher percentage of CD19+ cells (P = .015) and stage IV disease (P = .008) predicted poor survival for patients with postchemotherapy effusions. Only FIGO stage retained significance as a predictor of OS (P = .035) in multivariate analysis. Chemokine receptors are expressed widely on leukocytes but rarely on carcinoma cells in ovarian carcinoma effusions, arguing against an autocrine chemokine pathway in this malignancy. Immune response parameters in ovarian cancer effusions are weak predictors of outcome.

Adenocarcinoma↗
PubMed2005

The AP-2gamma transcription factor is upregulated in advanced-stage ovarian carcinoma.

OBJECTIVE: To analyze the expression of the AP-2gamma transcription factor in ovarian borderline tumors, early-stage ovarian carcinoma and advanced-stage ovarian carcinoma, and to evaluate its prognostic role in advanced-stage tumors. METHODS: Sections from 14 normal ovaries, 75 borderline tumors, 22 FIGO stage I invasive ovarian carcinomas, and 306 advanced-stage (FIGO stages II-IV) ovarian carcinomas (42 primary tumors, 62 solid metastases, 202 effusions) were evaluated for expression of the transcription factor AP-2gamma using immunohistochemistry. Sixty-three effusions and two cell lines (SKOV-3 and OVCAR-3) were additionally studied using immunoblotting. The prognostic role of AP-2gamma in advanced-stage carcinomas was analyzed. RESULTS: AP-2gamma was detected in the nucleus of tumor cells in 28/75 (37%) borderline tumors, 13/22 (59%) FIGO stage I carcinomas, and 255/306 (83%) advanced-stage carcinomas (P < 0.001, Chi-square test). Benign ovaries were uniformly negative. Expression was largely limited to carcinoma cells in effusions. Solid lesions and effusions from advanced-stage carcinomas showed comparable expression. Immunoblotting showed AP-2gamma expression in 59/61 effusions and both cell lines. AP-2gamma expression did not correlate with survival. CONCLUSIONS: AP-2gamma expression is upregulated in advanced-stage ovarian carcinoma compared to early-stage carcinomas, borderline tumors, and the ovarian surface epithelium, and AP-2gamma is specifically localized to cancer cells in effusions, suggesting a role in tumor progression. The lack of predictive value for this transcription factor in advanced-stage disease may be related to its frequent expression.

Adult↗
PubMed2005

Amplification of a chromatin remodeling gene, Rsf-1/HBXAP, in ovarian carcinoma.

A genomewide technology, digital karyotyping, was used to identify subchromosomal alterations in ovarian cancer. Amplification at 11q13.5 was found in three of seven ovarian carcinomas, and amplicon mapping delineated a 1.8-Mb core of amplification that contained 13 genes. FISH analysis demonstrated amplification of this region in 13.2% of high-grade ovarian carcinomas but not in any of low-grade carcinomas or benign ovarian tumors. Combined genetic and transcriptome analyses showed that Rsf-1 (HBXAPalpha) was the only gene that demonstrated consistent overexpression in all of the tumors harboring the 11q13.5 amplification. Patients with Rsf-1 amplification or overexpression had a significantly shorter overall survival than those without. Overexpression of Rsf-1 gene stimulated cell proliferation and transform nonneoplastic cells by conferring serum-independent and anchorage-independent growth. Furthermore, Rsf-1 gene knockdown inhibited cell growth in OVCAR3 cells, which harbor Rsf-1 amplification. Taken together, these findings indicate an important role of Rsf-1 amplification in ovarian cancer.

Carcinoma↗
PubMed2005

Identification and characterization of membralin, a novel tumor-associated gene, in ovarian carcinoma.

Identification of new genes in cancer is the key to understand the molecular basis of tumor development as well as provide potential diagnostic markers and therapeutic targets. A novel gene, membralin (GeneBank accession number: DQ005958), was cloned from a human ovarian cancer cell line. Human membralin is unique and does not share significant sequence homology with other human genes, only membralins of other species. The gene contains 11 exons which encode at least two spliced variants in human cancer. The long form of membralin (membralin-1) comprises all 11 exons, encoding a protein of 620-amino acids long and the short form of membralin (membralin-3) contains all exons except for exon 10, encoding a protein of 408 amino acids. Expression of different membralin isoforms depends on tissue type. The long form, membralin-1, is expressed in ovarian and colorectal carcinomas but not in breast or pancreatic carcinomas, which express only the short splice form, membralin-3. Membralin-1-GFP fusion protein demonstrates exclusive cytoplasmic localization. Based on quantitative real-time PCR, in situ hybridization and Western blot analysis, membralin was highly expressed in ovarian serous carcinomas as compared to ovarian surface epithelium (P<0.001). Ovarian carcinomas in effusions demonstrated a significantly higher level of membralin expression than in solid tumors (P<0.001). In conclusion, these findings represent the first characterization of human membralin and suggest that membralin is a novel tumor-associated marker in ovarian serous carcinomas.

Amino Acid Sequence↗
PubMed2005

Variation in gene expression patterns in effusions and primary tumors from serous ovarian cancer patients.

BACKGROUND: While numerous studies have characterized primary ovarian tumors, little information is available regarding expression patterns of metastatic sites of this cancer. To define sets of genes that distinguish primary and metastatic ovarian tumors, we used cDNA microarrays to characterize global gene expression patterns in 38 effusions (28 peritoneal, 10 pleural) and 8 corresponding primary ovarian tumors, and searched for associations between expression patterns and clinical parameters. RESULTS: We observed multidimensional variation in expression patterns among the cancers. Coordinate variation in expression of genes from two chromosomal regions, 8q and 19q, was seen in subsets of the cancers indicating possible amplifications in these regions. A set of 112 unique genes of known function was differentially expressed between primary tumors and effusions using supervised analysis. Relatively few differences were seen between effusions isolated from the pleural and peritoneal cavities or between effusions from patients diagnosed with stage III and stage IV cancers. A set of 84 unique genes was identified that distinguished high from lower grade ovarian cancers. The results were corroborated using immunocytochemistry, mRNA in situ hybridization, and immunoblotting. CONCLUSION: The extensive variation in expression patterns observed underscores the molecular heterogeneity of ovarian cancer, but suggests a similar molecular profile for ovarian carcinoma cells in serosal cavities.

Adult↗
PubMed2005

Mitogen-activated protein kinase expression and activation does not differentiate benign from malignant mesothelial cells.

BACKGROUND: In vitro studies of malignant mesothelioma (MM) cells have suggested activation of mitogen-activated protein kinase (MAPK) in response to asbestos exposure. The objective of this study was to investigate protein expression (level) and phosphorylation status (activity) of the extracellular-regulated kinase (ERK), the c-Jun amino-terminal kinase (JNK), and the high-osmolarity glycerol response kinase (p38) in vivo through the analysis of fresh frozen reactive mesothelium (RM) and MM specimens. METHODS: MAPK levels were analyzed in 36 fresh-frozen MM specimens (32 effusions, 4 biopsies) and in 14 RM specimens (all effusions) using immunoblotting with antibodies detecting the total (pan-) and activated (phospho-) fraction (p-) of ERK, JNK, and p38. Values for pan-MAPK and p-MAPK expression and the p-MAPK/pan-MAPK ratio in MM and RM specimens were compared. Results were corroborated using immunocytochemistry for p-ERK, p-JNK, and p-38 in selected specimens. RESULTS: Pan-ERK, pan-JNK, and pan-p38 expression was found frequently in both MM specimens (35 of 36 specimens) and RM specimens (14 of 14 specimens) using immunoblotting, with comparable findings for activated p-p38 (34 of 36 MM specimens, 13 of 14 RM specimens). Activation of p-ERK (27 of 36 MM specimens, 10 of 14 RM specimens) and p-JNK (25 of 36 MM specimens, 10 of 14 RM specimens) was less frequent. Pan-ERK (P = 0.016), pan-JNK (P = 0.004), pan-p38 (P = 0.012), and p-ERK (P = 0.02) expression levels were higher in MM specimens from female patients. Pan-p38 expression levels also were higher in peritoneal MM specimens (P = 0.019). MM and RM showed similar MAPK expression, activation, and activation ratios (Mann-Whitney test; P > 0.05). Immunocytochemistry localized MAPK to MM and RM cells. CONCLUSIONS: The current results provided the first evidence of in vivo activation of MAPK in clinical MM and RM. The similar values in these two cell types suggest that MAPK may not be involved in the transformation of benign to malignant mesothelium, thus bringing into question the validity of using MAPKs as molecular therapeutic targets in patients with MM.

Adult↗
PubMed2005

Expression of xeroderma pigmentosum A protein predicts improved outcome in metastatic ovarian carcinoma.

BACKGROUND: The nucleotide excision repair (NER) proteins repair DNA adducts due to xenobiotics and cancer chemotherapy. The authors hypothesized that expression of the NER protein xeroderma pigmentosum A (XPA) would be reduced in a clinically significant fashion in metastatic ovarian carcinoma. METHODS: Malignant effusion specimens were studied so that there was a uniform metastatic ovarian carcinoma population for study. XPA protein expression was analyzed by immunocytochemistry in 142 effusion specimens (109 peritoneal specimens, 33 pleural specimens) from 125 patients. Specimens were obtained at diagnosis (n = 76), and at disease recurrence (n = 66). Patients in the latter group received platinum-based chemotherapy. RESULTS: XPA was expressed in cancer cells in 136 of the 142 (96%) effusion specimens. Strongest expression occurred in leukocytes and reactive mesothelial cells. XPA expression did not correlate with treatment status, effusion site, International Federation of Gynecology and Obstetrics stage, histologic grade, or the extent of residual disease. More effusion tumor cells from patients with a complete response to chemotherapy expressed XPA compared with those with a partial or no response (P = 0.03, chi(2) test). Patients with recurrent disease with XPA expressed in > 25% of tumor cells had better progression-free survival (PFS) by univariate analysis (median = 0 vs. 11 months, P < 0.001; 95% confidence interval [CI], 1-5, 8-14) and overall survival (OS; median = 24 vs. 34 months, P = 0.04; 95% CI, 17-31, 24-44). XPA was the only predictor of PFS outcome by multivariate analysis (P = 0.03). CONCLUSIONS: The results of the current study showed that XPA was widely expressed in metastatic ovarian carcinoma effusion specimens and in the cells of the effusion microenvironment. Paradoxically, XPA expression was associated with better response to chemotherapy and predicted better PFS and OS.

Adenocarcinoma, Clear Cell↗
PubMed2005

Laminin-induced signaling in tumor cells.

Laminin is the main non-collagenous glycoprotein found in the basement membrane. The various laminin isoforms are involved in many physiological and pathological processes, including cancer dissemination. The interaction of cancer cells with laminin was identified as a key event in tumor invasion and metastasis. Laminin effects are mediated by laminin receptors that are divided into two groups: integrin and non-integrin receptors. Activation of a specific signal transduction pathway in the cell depends on various factors and may be altered when normal tissue becomes neoplastic. Laminin signals via multiple signal transduction pathways involving various components such as G-proteins, intracellular calcium, phospholipase D, mitogen activated protein kinases, phosphatases, focal adhesion kinase, small GTPases of the Rho family, and cytoskeleton components. This review focuses on the role of laminin in tumor progression, its signaling via the non-integrin 67kDa laminin receptor and via integrins and the reciprocal relations between these receptors in certain tumors.

Animals↗
PubMed2005

Snail, Slug, and Smad-interacting protein 1 as novel parameters of disease aggressiveness in metastatic ovarian and breast carcinoma.

BACKGROUND: It was demonstrated previously that the Snail family of transcription factors and Smad-interacting protein 1 (Sip1) regulate E-cadherin and matrix metalloproteinase 2 (MMP-2) expression, cellular morphology, and invasion in carcinoma. For the current study, the authors analyzed the relation between the expression of Snail, Slug, and Sip1; the expression of MMP-2 and E-cadherin; and clinical parameters in patients with metastatic ovarian and breast carcinoma. METHODS: One hundred one fresh-frozen, malignant effusions from patients who were diagnosed with gynecologic carcinomas (78 ovarian carcinomas and 23 breast carcinomas) were studied for mRNA expression of Snail, Slug, Sip1, MMP-2, and E-cadherin using reverse transcriptase-polymerase chain reaction analysis. Snail mRNA and E-cadherin protein expression levels also were studied in ovarian carcinoma effusions using in situ hybridization and immunocytochemistry. The results were analyzed for possible correlation with clinicopathologic parameters in both tumor types. RESULTS: E-cadherin mRNA expression was lower in breast carcinoma (P = 0.001), whereas Snail expression was higher (P = 0.003). The Snail/E-cadherin ratio (P < 0.001) and the Sip1/E-cadherin ratio (P = 0.002) were higher in breast carcinomas. Sip1 mRNA expression (P < 0.001) and Slug mRNA expression (P < 0.001) were correlated with the expression of MMP-2 in ovarian carcinomas. The Sip1/E-cadherin ratio was higher in primary ovarian carcinomas at the time of diagnosis compared with postchemotherapy ovarian carcinoma effusions (P = 0.003), higher in Stage IV tumors compared with Stage III tumors (P = 0.049), and higher in pleural effusions compared with peritoneal effusions (P = 0.044). In a univariate survival analysis of patients with ovarian carcinoma, a high Sip1/E-cadherin ratio predicted poor overall survival (P = 0.018). High E-cadherin mRNA expression predicted better disease-free survival (P = 0.023), with a similar trend for a low Slug/E-cadherin ratio (P = 0.07). High Snail mRNA expression predicted shorter effusion-free survival (P = 0.008), disease-free survival (P = 0.03), and overall survival (P = 0.008) in patients with breast carcinoma. CONCLUSIONS: Transcription factors that regulate E-cadherin were expressed differentially in metastatic ovarian and breast carcinoma. Snail may predict a poor outcome in patients who have breast carcinoma metastatic to effusions. E-cadherin expression generally was conserved in effusions from patients with ovarian carcinoma, but the subset of patients with postulated Sip1-induced repression of this adhesion molecule had a significantly worse outcome. This finding was in agreement with the stronger suppression of E-cadherin by Snail and Sip1 in breast carcinoma effusions, a clinical condition associated with extremely poor survival.

Adenocarcinoma, Clear Cell↗
PubMed2005

Risk markers of oral cancer in clinically normal mucosa as an aid in smoking cessation counseling.

PURPOSE: Quitting smoking may prevent oral cancer. Behavioral intervention to quit smoking may be more efficient if persons are assigned an individual risk of cancer. PATIENTS AND METHODS: In this prospective study, we provided counseling and behavioral intervention toward smoking cessation, supplemented by genetic analyses in clinically normal oral mucosa of heavy smokers. Measurement of serum cotinine was used to assess changes in smoking habits. RESULTS: In cytologic scrapings from 275 heavy smokers with clinically normal mucosa, we found tetraploidy in four and aneuploidy in 19 persons (23 of 275; 8%). Twenty one (91%) of 23 persons with aneuploidy had quit or reduced their smoking habits at the 3-month follow-up, 20 (87%) of 23 persons had done so at 12 months, and 21 (91%) of 23 persons had done so at 24 months. Fifty-one (20%) of the 252 persons without genetic changes in their mucosa had quit or reduced their tobacco habits at the 3-month follow-up, 23 (9%) had done so at 12 months, and 17 (7%) had done so at 24 months (P < .001). After 24 months, normalization of DNA content to diploidy was observed in two of four persons with tetraploid (50%), and in 11 of 19 persons (58%) with aneuploid scrapings. One patient developed an oral carcinoma in the floor of the mouth: this patient had an aneuploid scraping obtained 43 months earlier and developed a leukoplakia 28 months before the carcinoma. CONCLUSION: Risk markers of oral cancer are present in clinically normal mucosa of heavy smokers, and such findings enhance the adherence to smoking cessation on counseling. Cytogenetic aberrations may normalize after quitting smoking.

Adult↗
PubMed2005

Apolipoprotein E is required for cell proliferation and survival in ovarian cancer.

Apolipoprotein E (ApoE) has been recently identified as a potential tumor-associated marker in ovarian cancer by serial analysis of gene expression. ApoE has long been known to play a key role in lipid transport, and its specific isoforms may participate in atherosclerogenesis. However, its role in human cancer is not known. In this study, apoE expression was frequently detected in ovarian serous carcinomas, the most common and lethal type of ovarian cancer. It was not detected in serous borderline tumors and normal ovarian surface epithelium. Inhibition of apoE expression using an apoE-specific siRNA led to G(2) cell cycle arrest and apoptosis in an apoE-expressing ovarian cancer cell line, OVCAR3, but not in apoE-negative cell lines. Furthermore, the phenotype of apoE siRNA-treated OVCAR3 cells was reversed by expressing engineered mutant apoE with introduced silent mutations in the siRNA target sequence. Expression of apoE in nuclei was significantly associated with a better survival in patients who presented peritoneal effusion at the time of diagnosis (5-year follow-up, P = 0.004). This study suggests a new role of apoE in cancer as apoE expression is important for the proliferation and survival in apoE-expressing ovarian cancer cells.

Apolipoproteins E↗
PubMed2005

Primary ovarian angiosarcoma presenting as malignant cells in ascites: case report and review of the literature.

Primary angiosarcoma of the ovary is a rare tumor, with less than 25 cases reported in the literature. These tumors are thought to arise from carcinosarcomas, teratomas or the ovarian vasculature, and occur at any age. The prognosis is dismal in the majority of cases. We present the case of a 19-year old female who presented with abdominal distention and abdominal pain. Tapping of peritoneal effusion showed groups of pleomorphic cells that were negative for epithelial and germ cell markers. Immunohistochemistry performed on the surgical specimen of the ovary, and subsequently on the effusion specimen showed staining for endothelial markers. The patient was treated post-operatively with chemotherapy, but died one year following diagnosis. This is the first reported case of an ovarian angiosarcoma that metastasized to the peritoneal cavity, with a resulting malignant effusion. Despite the rarity of metastasis from gynecological sarcomas in effusions, this possibility needs to be included in the differential diagnosis of malignant effusions that are negative for epithelial and germ cell markers.

Adult↗
PubMed2005

Quantitative analysis of integrin expression in effusions using flow cytometric immunophenotyping.

We have previously shown that flow cytometric (FCM) immunophenotyping is a useful adjunct to morphology, in the diagnosis of serous effusions. The objective of the present study was to evaluate the possible application of FCM to quantitative analysis of adhesion molecule expression in this clinical setting. Fresh frozen cells from 67 effusions underwent quantitative analysis of alphaV, alpha6, beta1, and beta3 integrin subunit expression, using FCM. Specimens were diagnosed as carcinoma (n = 48), reactive (n = 12), or malignant mesothelioma (MM; n = 7) using morphology and, in selected cases, immunocytochemistry prior to FCM analysis. Antibodies against established epithelial, lymphoid, and mesothelial cell epitopes (Ber-EP4, anti-epithelial membrane antigen; (EMA), anti-CD45, anti-CD14, and anti-CD15) completed the panel. Results (percentage of cells expressing the antigen) were analyzed for relationship with the morphologic diagnosis. Frequent expression of the alphaV, alpha6, and beta1 subunits was seen in all diagnostic groups, with significantly higher expression of the alpha6 subunit in MM (P = 0.029, Kruskal-Wallis H test). The beta3 integrin subunit was not detected in any of the specimens. Ber-EP4 and CD15 expression was significantly higher in carcinomas compared with reactive effusions and MM (P < 0.001 and P = 0.001, Kruskal-Wallis H test), and EMA expression was higher in carcinomas and MM, compared with reactive specimens (P < 0.001, Kruskal-Wallis H test). In conclusion, FCM is an efficient tool for quantitative analysis of adhesion molecules in effusions. The high alpha6 integrin subunit expression in MM suggests involvement of this receptor in tumor attachment to laminin. The frequent expression of the alphaV and beta1 subunits support attachment to fibronectin and vitronectin as the major ECM ligands in body cavities.

Ascitic Fluid↗
PubMed2005

Differential expression of the 67 kilodalton laminin receptor in epithelioid malignant mesothelioma and carcinomas that spread to serosal cavities.

Expression of the 67-kd laminin receptor (67-kd LR) has been reported in a wide range of carcinomas, in many of which it correlated with poor differentiation, metastasis, disease progression, and poor survival. Malignant mesothelioma (MM) is a locally aggressive and highly lethal tumor of serosal cavities that is rarely associated with clinically detectable metastasis to distant organs. The aim of this study was to analyze the expression of the 67-kd LR in epithelioid MM and carcinomas in effusions. Effusions from patients diagnosed with ovarian (=24) and breast (=38) adenocarcinomas and MM (=24) (total = 86) were analyzed for 67-kd LR protein expression, using immunocytochemistry. The 67-kd LR mRNA expression was additionally analyzed in 21 MM effusions using reverse transcription-polymerase chain reaction (RT-PCR). Protein expression of the 67-kd LR was frequently detected in carcinomas (19/24 ovarian tumors, 79%; 15/38 breast tumors, 39%), but was rare in MM (2/24 cases, 8%), despite the presence of mRNA transcripts for the receptor in all 21 specimens studied using RT-PCR. Nine benign effusions that were additionally studied for protein expression were uniformly negative, as were all reactive mesothelial cells in malignant effusions. Our results suggest that the 67-kd LR may aid in the differential diagnosis between metastatic carcinoma, mainly of ovarian origin, and MM. They additionally suggest that the failure of MM to express the 67-kd LR protein, as opposed to the frequent expression in carcinomas with proven metastatic capacity, may be one of the factors contributing to the reduced ability of the former tumor to metastasize to distant organs.

Adenocarcinoma↗