Cytoplasm Of Malignant Cells Research Articles

Detection of FOXP-3 Expression in a Sample of Iraqi Cervical Cancer Patients Using Immunohistochemistry Technique

This paper aims to find out if FOXP-3 was expressed in samples from Iraqi cervical cancer patients. Expression of FOXP-3 was detected in 55 cervical tissue samples by immunohistochemistry. Since thirty-five cases of aggressive cervical cancer were included, along with 20 normal samples used as controls. The nucleus and cytoplasm levels of FOXP-3 were counted, considering the ratio of positive cells and intensity. FOXP3 cytoplasmic staining was found in 27 out of 35 cases. Only 11 out of 35 samples displayed nuclear lymphocyte staining. Furthermore, four samples expressed this marker in both the nuclear and cytoplasm of the cervical cells. There is a highly significant difference in FOXP3 expression in the cytoplasm of malignant cells and lymphocytes compared to normal samples. Seven samples out of 11 cells correlated with lymph vascular invasion. These results show that tissue positive FOXP-3 possesses a possible diagnostic marker for Iraqi cervical cancer. FOXP3 is significantly expressed in cancer cells, and lymphocyte infiltrates [T-reg] compared to normal.

Polymorphic Variants in 5'-UTR Regions of the RAD51 Gene are Associated With RAD51 Expression and Triple-Negative Breast Cancer (TNBC): A Case-Control Study.

Breast cancer is a heterogeneous disease at morphologic and molecular levels, which is considered the most commonly occurring cancer in women. RAD51, a DNA-repairing protein, involves homologous recombination and has a vital role in genome stability. Polymorphism of the RAD51 gene, and its overexpression, has been proposed to be associated with the development of breast cancer. Overexpression of RAD51 in many types of human cancer including metastatic breast cancer may signify its potential use as a biomarker. Considering the numerous reports on the role of the 5'-UTR-RAD51 polymorphism in breast cancer, this study aimed to investigate the utility of RAD51 gene expression and its variants G135C and G172T as a possible foretelling factor of breast cancer development. DNA sequencing and immunohistochemistry of RAD51 were conducted on 103 samples from patients diagnosed with sporadic breast cancer and 80 samples from a control group. The results demonstrated that the RAD51 variants, G135C and G172T, were significantly presented in the breast cancer tissue compared with the control group. RAD51 expression was mainly shown in the cytoplasm of malignant cells (56% of cases) and significantly correlated with p53 and G135C, C135C variants. Moreover, the occurrence of the G172T variant was significantly associated with the expression of estrogen receptor. Interestingly, 21/26 (81%) of the triple-negative breast cancer showed G135C and C135C genotypes that were significantly associated with the expression of RAD51 (73%). In conclusion, the G135C and C135C variants together with the cytoplasmic expression of RAD51 may have clinical potential as a prognostic predictor for breast cancer development and aggressiveness.

Chemosensitization of Prostate Carcinoma Cells with a Receptor-directed Smac Conjugate.

Second mitochondrial activator of caspase (Smac) is a short mitochondrial peptide. When released from the mitochondria into the cytoplasm, it binds to inhibitor of apoptotic proteins (IAPs) within the cytoplasm and prevents them from inhibiting apoptosis. Delivery of external synthetic Smac peptide into the cytoplasm of malignant cells could greatly improve the efficiency of apoptosis-inducing chemotherapeutic agents. In our study different conjugates based on the seven N-terminal amino acids AVPIAQK of Smac (SmacN7) were produced to obtain a cytoplasm-directed Smac variant. SmacN7 and a point mutant (AVPKAQK) were coupled either to rhodamine alone or to both rhodamine and undecylic aldehyde, which is an antagonist of the Lily-of-the-valley fragrance receptor. The fifth conjugate consisted of rhodamine coupled only to undecylic aldehyde, without SmacN7. The uptake of these five conjugates into three different human cell lines was characterized and quantified by confocal laser scanning microscopy and flow cytometry. A caspase apoptosis assay was performed for cells incubated with the five different conjugates after induction of apoptosis. The coupling of undecylic aldehyde to SmacN7 increased the cellular uptake of the correct and mutant conjugates. Caspase 3/7 apoptosis tests after induction of apoptosis with staurosporine or UV irradiation showed that the coupling of SmacN7 with undecylic aldehyde resulted in a greatly increased adjuvant pro-apoptotic effect compared to the separate components and a mutant SmacN7 peptide sequence in the LNCaP prostate carcinoma cells compared to the benign prostate hyperplasia (BPH) cells and the human embryonal kidney (HEK) cells.

Aberrant Expression of N-Glycolyl GM3 Ganglioside in Hepatocellular Carcinoma

Representative microphotograph regarding the aberrant expression of N-glycolyl GM3 ganglioside (NeuGcGM3) in hepatocellular carcinoma. The preferential accumulation of NeuGcGM3 in a variety of malignant tumors, when compared with healthy tissues, became this molecule as attractive target for cancer immunotherapy. In the present sample, the expression of NeuGcGM3 was located in both cell membrane and cytoplasm of malignant cells (brown color) (Figure 1). Additionally, a strong expression of this ganglioside in perinuclear areas was evidenced. This fact could be related with the synthesis of NeuGcGM3 in the Golgi apparatus and the posterior intracellular movement of this molecule within the different subcellular compartments to the plasma membrane. The immunostaining was performed with the 14F7 monoclonal antibody, a highly specific IgG1 against NeuGcGM3. The immunohistochemical detection of NeuGcGM3 allow considering the potential selection of this patient for specific therapy with racotumomab or NGcGM3/VSSP molecular cancer vaccines. Cell nuclei are observed in blue color (Mayer’s hematoxylin). White bar=100 μm.

Hypomethylation of the thymosin β(10) gene is not associated with its overexpression in non-small cell lung cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide and is usually associated with a late diagnosis and a poor prognosis. Thymosin β(10) (TMSB10) is a monomeric actin sequestering protein that regulates actin cytoskeleton organization. The aberrant TMSB10 expression has been implicated in the pathogenesis of human cancers. However, its role in carcinogenesis is still controversial. To better understand the role of TMSB10 in lung tumorigenesis and its regulatory mechanism, we examined the methylation status and expression of the TMSB10 gene in non-small cell lung cancers (NSCLCs) using methylation-specific PCR (MSP) and immunohistochemistry (IHC), respectively. MSP analysis showed that the TMSB10 promoter was already unmethylated in most tumor tissues and became demethylated in 20 (14.4%) of the 139 NSCLCs. TMSB10 hypomethylation was not significantly correlated with the clinicopathological features. IHC showed that the TMSB10 protein was strongly expressed in the cytoplasm of malignant cells and its overexpression was detected in 50.0% of the tumor tissues compared to normal tissues. TMSB10 overexpression was frequently observed in sqaumous cell carcinomas compared to adenocarcinomas with border line significance (P = 0.072). However, TMSB10 methylation status was not linked to its overexpression. Collectively, these results suggest that TMSB10 hypomethylation may be a frequent event in NSCLCs, but it may not be a common mechanism underlying TMSB10 overexpression. However, further studies with large numbers of patients are needed to confirm our findings.

STAT3 and apoptosis regulators: Bak and Bcl-xL in endometrioid adenocarcinomas of different estrogen receptor-𝛂 immunoprofile

Estrogen receptor (ER) is a major feature of endometrioid adenocarcinoma. It has a significant impact on constitution of estrogen-responsiveness of this endometrial malignancy, in which STAT3 (signal transducer and activator of transcription) becomes hyperactivated. The aim of our study was to detect immunohistochemically and compare expressions of STAT3 with apoptosis regulators (Bak and Bcl-xL) in regard to different pathological features and variably pronounced ER-α immunoprofile in 78 endometrioid adenocarcinomas. STAT3 was abundantly detected in nuclei of cancer cells in 54 cases, thus pointing at its activation as an universal nuclear transcriptional factor. Bcl-xL and Bak were expressed in cytoplasm of malignant cells in 62 and 20 cancers, respectively. STAT3 correlated both with Bcl-xL (p = 0.001, r = 0.365) and Bak (p < 0.001, r = 0.436) in all of endometrioid adenocarcinomas and variably in different subgroups of these tumours segregated in regard to grading, staging and patients' age. Remarkably, only ER-α positive cancers retained these correlations in opposition to ER-α negative tumours with negativity defined as an immunoreactivity below 10%. ER-α receptor probably enhances interactions between STAT3 and Bcl-xL to be present in statistically significant manner. Presence of ER-α receptor seems to be crucial for relationships among Bcl-xL and STAT3 to occur in endometrioid adenocarcinomas.

Abstract 4816: Overexpression of thymosin β10 gene is not mediated by DNA methylation in non-small cell lung cancer

Abstract Lung cancer is the leading cause of cancer-related deaths worldwide and is usually associated with a late diagnosis and a poor prognosis. Thymosin β10 (TMSB10) is monomeric actin sequestering protein to regulate actin cytoskeleton organization. The aberrant TMSB10 expression has been implicated in the pathogenesis of human cancers. However, its role in carcinogenesis is still controversial. To better understand the role of TMSB10 in lung tumorigenesis and its regulatory mechanism, we have examined the methylation status and expression of the TMSB10 gene in non-small cell lung cancers (NSCLCs) using methylation-specific PCR (MSP) and immunohistochemistry (IHC), respectively. MSP analysis showed that TMSB10 promoter was almost unmethylated in tumor tissues and became to be hypomethylated in 7 out of 139 (5.0%) NSCLCs. However, there is no significant association of TB10 demethylation with clinicopathologic features. IHC showed that TMSB10 protein was strongly expressed in the cytoplasm of malignant cells and its overexpression was detected in 15 of 30 (50.0%) the tumor tissues compared to normal tissues. Moreover, TMSB10 overexpression was frequently observed in sqaumous cell carcinomas compared to adenocarcinomas with border line significance (P = 0.072), but its overexpression was not associated with the methylation status of TMSB10 gene. Collectively, these results suggest that TMSB10 overexpression may be a frequent event in the progression of NSCLC, but DNA methylation may not involve in TMSB10 overexpression. However, further studies with a large number of cases are needed to confirm our findings. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4816. doi:10.1158/1538-7445.AM2011-4816

Molecular characterization of EGFR, PDGFRA and VEGFR2 in cervical adenosquamous carcinoma

BackgroundAdenosquamous carcinoma of the uterine cervix is an infrequent but aggressive subtype of cervical cancer. A better understanding of its biological behaviour is warranted to define more accurate prognosis and therapeutic targets. Currently, the blockage of receptor tyrosine kinase (RTKs) activity is an efficient therapeutic strategy for many different cancers. The objective of this study was to investigate EGFR, PDGFRA and VEGFR2 RTKs overexpression and activating gene mutations in a cohort of 30 adenosquamous carcinomas of the uterine cervix.MethodsEGFR, PDGFRA and VEGFR2 immunohistochemistry was performed in all samples, followed by DNA isolation from the gross macroscopically dissection of the neoplastic area. Screening for EGFR (exons 18–21) and PDGFRA (exons 12, 14 and 18) mutations was done by PCR – single-strand conformational polymorphism (PCR-SSCP).ResultsDespite the presence of EGFR immunohistochemical positive reactions in 43% (13/30) of the samples, no EGFR activating mutations in the hotspot region (exons 18–21) were identified. A silent base substitution (CAG>CAA) in EGFR exon 20 at codon 787 (Q787Q) was found in 17 cases (56%). All PDGFRA immunohistochemical reactions were positive and consistently observed in the stromal component, staining fibroblasts and endothelial cells, as well as in the cytoplasm of malignant cells. No activating PDGFRA mutations were found, yet, several silent mutations were observed, such as a base substitution in exon 12 (CCA>CCG) at codon 567 (P567P) in 9 cases and in exon 18 (GTC>GTT) at codon 824 (V824V) in 4 cases. We also observed the presence of base substitutions in intron 14 (IVS14+3G>A and IVS14+49G>A) in two different cases, and in intron 18 (IVS18-50insA) in 4 cases. VEGFR2 positivity was observed in 22 of 30 cases (73.3%), and was significantly associated with lack of metastasis (p = 0.038).ConclusionThis is the most extensive analysis of EGFR, PDGFRA and VEGFR2 in cervical adenosquamous carcinomas. Despite the absence of EGFR and PDGFRA activating mutations, the presence of overexpression of these three important therapeutic targets in a subset of cases may be important in predicting the sensitivity of adenosquamous carcinoma to specific anti-RTKs drugs.

Expressão da MMP-9 e do VEGF no câncer de mama: correlação com outros indicadores de prognóstico

to analyze the expression of matrix metalloproteinase-9 (MMP-9) and of vascular endothelial growth factor (EVGF) in a group of patients with primary breast cancer, and correlate them to one another and with other prognostic indicators. transversal study that has analyzed the expression of MMP-9 and of VEGF in 88 consecutive cases of primary breast tumors. The samples were obtained from patients with primary breast cancer, submitted to surgical treatment in the Clinical Hospital of Porto Alegre of the Universidade Federal do Rio Grande do Sul, from January 2000 to December 2004. An immunohistochemical technique has been applied, using the avidin-biotin-peroxidase complex to evaluate the antigen immunoreactions in the tumors. The qualitative expression of proteins has been assessed through the observation of the brownish stain intensity of antibodies in the cytoplasm of malignant cells, when at least one of the tumoral cells presented clear and unequivocal staining with each of those markers. To determine the qualitative score (0=absent, 1=weak, 2=average and 3=strong), the stronger cytoplasmatic staining intensity on the glass slide has been taken into consideration, independently of the stained cells. The quantitative expression was determined by the average percentage of stained cells, observed in at least ten microscopic fields. The MMP-9 and VEGF final quantification expression has been done by the application of the HSCORE=Sigma[(I+1)]xPC, where I and PC represent the staining intensity and the percentage of stained cells, respectively. MMP-9 and VEGF presented a significant correlation in the tumors studied. The final expression has shown a median score of 180 and 190, respectively. When MMP-9 and VEGF expression were compared with the variables 'age', 'tumoral diameter', 'histological type', 'histological grade', 'axillary lymph node' and 'vascular invasion', it was impossible to find any significant correlation. Compared to one another, MMP-0 and VEGF have presented a positive correlation (rho=0.23; p=0.03). The axillary lymph node positivity has presented a positive correlation with the larger tumoral diameter (2.7+/-1.1 cm; p<0.01) and with the presence of vascular invasion (84.1%; p<0.01). The present results do not show correlation between the MMP-9 and VEGF with the selected prognostic indicators, but shown a significant correlation between one another.

Tumor-derived matrix metalloproteinase-13 (MMP-13) correlates with poor prognosis of invasive breast cancer

BackgroundExperimental evidence suggests that matrix metalloproteinase-13 (MMP-13) protein may promote breast tumor progression. However, its relevance to the progression of human breast cancer is yet to be established. Furthermore, it is not clear whether MMP-13 can be used as an independent breast cancer biomarker. This study was conducted to assess the expression profile of MMP-13 protein in invasive breast carcinomas to determine its diagnostic and prognostic significance, as well as its correlation with other biomarkers including estrogen receptor (ER), progesterone receptor (PR), Her-2/neu, MMP-2, MMP-9, tissue inhibitor of MMP-1 and -2 (TIMP-1 and TIMP-2).MethodsImmunohistochemistry (IHC) was performed on paraffin-embedded tissue microarray containing specimens from 263 breast carcinomas. The intensity and the extent of IHC were scored by pathologists in blind fashion. The correlation of the gene expression profiles with patients' clinicopathological features and clinical outcomes were analyzed for statistical significance.ResultsMMP-13 protein was detected in the cytoplasm of the malignant cells and the peritumoral stromal cells. MMP-13 expression by tumor cells (p < 0.001) and stromal fibroblasts (p <0.001) both correlated with carcinoma infiltration of lymph nodes. MMP-13 also correlated with the expression of Her-2/neu (p = 0.015) and TIMP-1 (p < 0.010), respectively in tumor cells. Tumor-derived, but not stromal fibroblast-derived, MMP-13 correlated with aggressive tumor phenotypes. Moreover, high levels of MMP-13 expression were associated with decreased overall survival. In parallel, the prognostic value of MMP-13 expressed by peritumoral fibroblasts seems less significant. Our data suggest that lymph node status, tumor size, Her-2/neu expression, TIMP-1 and MMP-13 expression in cancer cells are independent prognostic factors.ConclusionTumor-derived, but not stromal fibroblast-derived, MMP-13 correlated with aggressive tumor phenotypes, and inversely correlated with the overall survival of breast cancer patients. MMP-13 may serve as an independent prognostic factor for invasive breast cancer patients. MMP-13 may be particularly useful as a prognostic marker when evaluated along with Her-2/neu and lymph node status.

Claudin-1 overexpression in melanoma is regulated by PKC and contributes to melanoma cell motility

Serial analysis of gene expression followed by pathway analysis implicated the tight junction protein claudin-1 (CLDN1) in melanoma progression. Tight junction proteins regulate the paracellular transport of molecules, but staining of a tissue microarray revealed that claudin-1 was overexpressed in melanoma, and aberrantly expressed in the cytoplasm of malignant cells, suggesting a role other than transport. Indeed, melanoma cells in culture demonstrate no tight junction function. It has been shown that protein kinase C (PKC) can affect expression of claudin-1 in rat choroid plexus cells, and we observed a correlation between levels of activated PKC and claudin expression in our melanoma cells. To determine if PKC could affect the expression of CLDN1 in human melanoma, cells lacking endogenous claudin-1 were treated with 200 nM phorbol myristic acid (PMA). PKC activation by PMA caused an increase in CLDN1 transcription in 30 min, and an increase in claudin-1 protein by 12 h. Inhibition of PKC signaling in cells with high claudin-1 expression resulted in decreased claudin-1 expression. CLDN1 appears to contribute to melanoma cell invasion, as transient transfection of melanoma cells with CLDN1 increased metalloproteinase 2 (MMP-2) secretion and activation, and subsequently, motility of melanoma cells as demonstrated by wound-healing assays. Conversely, knockdown of CLDN1 by siRNA resulted in the inhibition of motility, as well as decreases in MMP-2 secretion and activation. These data implicate claudin-1 in melanoma progression.

Expressions of human telomerase mRNA component (hTERC) and telomerase reverse transcriptase (hTERT) mRNA in effusion cytology.

Telomerase is a ribonucleoprotein enzyme that synthesizes telomeric DNA onto chromosomal ends. Its activity has been reported to be a novel diagnostic marker of malignant potential. However, no study has investigated the diagnostic importance of the expressions of human telomerase mRNA component (hTERC) and telomerase reverse transcriptase (hTERT) mRNA in effusion cytology. We investigated the expressions of hTERC and hTERT using in situ hybridization in 20 malignant cytologic specimens from 20 patients with adenocarcinomas disseminating into the pleura or peritoneum, and 16 benign cytologic specimens in pleural or peritoneal fluid (including reactive mesothelial cells) from 16 patients with non-neoplastic diseases. Expressions of hTERC and hTERT mRNA were detected in 95% and 90% of the 20 malignant cytology specimens, respectively, and were apparent within the cytoplasm of malignant cells. However, no expression was detected in reactive mesothelial cells in the 16 benign cytologic specimens. The expressions of hTERC and hTERT mRNA would appear to be a useful addition to cytology examination for diagnosis based on effusion cytology.

Production and characterisation of a novel chicken IgY antibody raised against C-terminal peptide from human thymidine kinase 1

Egg yolk is a good source of highly specific antibodies against mammalian antigens because of the phylogenetic distance between birds and mammals. Chicken egg yolk immunoglobulins (IgY) were generated to a synthetic 31-amino acid peptide from the C-terminal of human HeLa thymidine kinase 1 (TK1) enzyme. The anti-TK1 IgY antibody was purified using affinity chromatography against the 31-amino acid peptide. The purified antibody inhibited the catalytic activity of the TK1 enzyme in the CEM TK1 + cells and recognized the 25-kDa subunit and tetrameric form of TK1, which has a p I value of 8.3. No immunoreaction was observed in CEM TK1 − cells. Western blot of the serum TK1 (S-TK1) also showed that only a single band was found in the serum of patients with malignancies. No band was seen in healthy serum. Furthermore, dot blots and enhanced chemiluminescence (ECL) detection of S-TK1 performed on sera of preoperative patients with gastric cancer (GC) ( n=31) and healthy controls ( n=62) showed that the levels of S-TK1 in the sera of cancer patients were significantly different ( P<0.01). Using ECL dot blots, 0.1 pg of TK1 in 3 μl sera could be detected. Immunohistostaining of tissues in the 11 advanced-stage cancer patients (four breast carcinomas, three hepatocarcinomas and four thyroid carcinomas) indicated that a strong staining of TK1 enzyme was found in the cytoplasm of malignant cells. No staining or weak staining was seen in normal tissues. We suggest that screening for TK1 using anti-TK1 IgY may be potentially useful for serological and immunohistochemical detection of TK1 as an early prognosis and for monitoring patients undergoing treatment.

Expression of p160erbB-3 and p185erbB-2 in prostatic intraepithelial neoplasia and prostatic adenocarcinoma.

Although prostatic adenocarcinoma is the most frequent malignancy among American men, little is known concerning the roles of growth factors, growth factor receptors, or proto-oncogene products in the development and progression of this malignancy. We examined and compared the expression and cellular distribution of the erbB-3 protein (p160erbB-3) and the erbB-2 protein (p185erbB-2) in various stages of development and progression of prostatic adenocarcinoma. Immunoperoxidase staining was used to determine the expression of p160erbB-3 and p185erbB-2 in benign prostatic epithelium, prostatic intraepithelial neoplasia, localized adenocarcinomas (pathologic stages B and C) as well as matching primary and lymph node lesions from patients with stage D adenocarcinoma. In order to test antibody specificity, we used Western blot analysis to examine the expression of p160erbB-3 and p185erbB-2 in selected prostatic adenocarcinomas. Within benign glands, immunostaining for p160erbB-3 or p185erbB-2 was strongest in the basal cells and was typically absent or weak in the luminal (secretory) cells. Expression of both proteins within luminal cells was localized to cell membranes. We examined the expression of p160erbB-3 and p185erbB-2 in the prostatic intraepithelial neoplastic lesions of 22 radical prostatectomy specimens. Like benign glands, the basal cells of these neoplastic lesions typically demonstrated strong to moderate immunostaining when stained with either antibody. In contrast to benign glands, moderate to strong immunostaining for p160erbB-3 and p185erbB-2 was frequently observed within the cytoplasm and cell membranes of the prostatic intraepithelial neoplastic luminal cells. p160erbB-3 and p185erbB-2 were detected within the malignant cells in 28 and 29 of 29 localized adenocarcinomas, respectively. Immunostaining with either antibody was typically moderate to strong in the malignant cells. Both proteins were expressed on the cellular membranes as well as in the cytoplasm of malignant cells. Immunostaining for p160erbB-3 was detected in the matching primary and metastatic lesions (lymph nodes) in 10 of 11 patients with stage D adenocarcinoma. Immunostaining for p185erbB-2 was detected in matching primary and metastatic lesions (lymph nodes) obtained from 16 patients with stage D adenocarcinoma. Western blot analysis confirmed the specificity of the antibodies. These results suggest that increased expression and changes in the subcellular distribution of both p160erbB-3 and p185erbB-2 represent early events in the development and progression of prostatic adenocarcinomas. The high expression and distribution of both p160erbB-3 and p185erbB-2 are retained both in advanced-stage primary and metastatic tumors.

Tumor Associated Glycoprotein-72 is Highly Expressed in Prostatic Adenocarcinomas

We examined the expression of two well-characterized oncofetal antigens, the tumor associated glycoprotein-72 (TAG-72) and carcinoembryonic antigen (CEA), in malignant prostatic tissues. Three specific monoclonal antibodies, B72.3, CC49 and CC83, were used to examine the expression of TAG-72. Immunoreactivity was detected in 63% of the malignant specimens using B72.3. CC49 and CC83 were more sensitive than B72.3 in detecting TAG-72 expression. Immunoreactivity was detected in approximately 80% of prostatic adenocarcinomas with CC49 or CC83. The pattern and localization of TAG-72 immunoreactivity were similar for the three antibodies with most immunoreactivity observed within the cytoplasm of malignant cells and within the lumens of malignant glands. TAG-72 immunoreactivity was not detected within benign epithelium or stroma, with the exception of focal epithelial expression in areas of acute prostatitis. The COL-1 antibody to CEA did not detect CEA in benign glands, stroma, or malignant cells of prostate specimens resected for prostatic adenocarcinoma. These results demonstrate that TAG-72, but not CEA, is frequently expressed in prostatic adenocarcinomas.

Expression of E-cadherin in normal, benign, and malignant tissues of female genital organs.

The expression of human E-cadherin in normal tissues and in benign and malignant tumors of female genital organs was examined immunohistochemically with a monoclonal antibody, HECD-1, specific for human E-cadherin. The normal tissues included the ovary, fallopian tube, uterine endometrium, uterine cervix, and vagina. E-cadherin was detected clearly in the cell-to-cell boundaries of both normal glandular and squamous epithelia obtained from those tissues. The tumor tissues consisted of 9 ovarian, 7 endometrial, and 4 cervical adenocarcinomas, 12 squamous cell carcinomas of the cervix, including 3 cervical intraepithelial neoplasms, and 5 mesenchymal tumors. E-cadherin also was detected in the cell-to-cell borders of all the epithelial tumors tested, with some reactivity in the cytoplasm of malignant cells, whereas mesenchymal tumors showed no expression. It is noteworthy that poorly differentiated areas of both the adenocarcinomas and squamous cell carcinomas showed less expression of E-cadherin. No difference in the expression of E-cadherin between the primary and metastatic lesions was detected in 10 sets of malignant tumors. E-cadherin may be an important factor among a variety of biologic events that occur during the process of metastasis. However, further studies are needed to clarify this.

Cytochemical analysis of acid hydrolases expression during phorbol diester (TPA)-driven differentiation of B-chronic lymphocytic leukaemia cells in vitro

Four acid hydrolases, acid phosphatase (AP), α-naphthyl acetate acid esterase (ANAE), β-glucuronidase (BG) and N-acetyl-β-glucosaminidase (NABG) were determined cytochemically in B-chronic lymphocytic leukaemia (B-CLL) cells exposed in vitro to the tumor promoter 12-O-tetradecanoyl phorbol 13 acetate (TPA). TPA, which has been previously shown to induce B-CLL cells to mature towards plasmacytoid cells, results in the progressive expression of the enzymes tested in the cytoplasm of malignant cells, in particular AP and ANAE. Furthermore, the sensitivity to inhibitors and the pattern of reactivity of ANAE provide evidence for an enzyme subtype normally restricted to plasma cells. Thus, acid hydrolases — some of which showing plasma cell type of activity — are expressed during B-CLL cells differentiation induced in vitro. These results confirm the value of cytochemistry in subtyping B-cell malignancies.

B-Cell Malignancy and Monoclonal Gammopathy, and Idiotype of Cell Surface and Serum Immunoglobulin

We studied cell surface membrane immunoglobulins (SmIg), intracytoplasmic Ig (CIg) and monoclonal Ig (M protein) in patients with the B-cell series malignancies; malignant lymphoma, chronic lymphocytic leukemia (CLL), Waldenström's macroglobulinemia (WM), multiple myeloma (MM), and monoclonal gammopathy (MG) associated with Sjögren's syndrome (SS). The patients were examined for idyotype (Id) determinants on the cell surface and in the cytoplasm of malignant cells as well as serum M proteins. Twenty-two patients had malignant lymphoma with monoclonal SmIg. The malignant cells of 11 patients contained CIg; four of these 11 patients had a small amount of serum M protein. SmIg of the IgM class was most frequent (12/22) and the lambda type light chain was predominant (kappa/lambda ratio = 4/8). By means of rabbit anti-Id antisera prepared against M proteins, Id determinants were demonstrated on the cell surface and in the cytoplasm of malignant cells as well as in the serum M proteins, indicating that the malignant cells proliferated monoclonally producing monoclonal IgM on the cell surface and in the cytoplasm and secreting it to the serum. Six CLL patients were included in our series; one manifested monoclonal IgM in the serum. The Id determinants of M protein was detected on the cell surface and in the cytoplasm of pathologic cells in the peripheral blood. Eight of ten WM patients were examined for SmIg; all had monoclonal SmIg on the surface of cells from peripheral blood or bone marrow. Id determinants were detected on the cell surface and in the cytoplasm of malignant cells in four WM patients. There were 42 patients with MM; 10 of them were examined for SmIg and three of these had monoclonal SmIg on plasma cells derived from the bone marrow. By immunofluorescent and mixed rosette methods, Id-bearing B (0-20%) and T cells (0-2%) were identified in the peripheral blood of MM patients who had no plasma cells in the peripheral blood. Our findings suggest that a monoclonal change may occur at the B-cell level and that Id-bearing T cells may exist as regulatory T cells. Ten SS patients had M proteins. Non-IgM class M proteins (2 IgG and 4 IgA) were more frequent than the IgM class (3 IgM). Four M proteins with rheumatoid factor (RF) activity were found among these 10 M proteins.(ABSTRACT TRUNCATED AT 400 WORDS)

Primary Kaposi’s Sarcoma of Lymph Nodes

An example of Kaposi's sarcoma with primary involvement of lymph nodes is reported. The patient, a woman, was admitted because of generalized lymphadenopathy and anemia. She was also known to have congestive heart failure of rheumatic origin. SMA-12 screening disclosed hypercalcemia on several occasions during her hospitalization. Levels of circulating parathormone and prostaglandins E2 and F were markedly increased. Total bone scan was negative for involvement by tumor. Electronmicroscopic examination of an involved lymph node disclosed secretory bodies in the cytoplasm of malignant cells and other cells, with clear indication of endothelial origin. The rarity of Kaposi's sarcoma with primary lymph nodal involvement in the United States is discussed. So far as is known by the authors, no example of Kaposi's sarcoma has been associated with hypercalcemia due to ectopic endocrine production.

LIPID DROPLETS IN THE CYTOPLASM OF MALIGNANT CELLS.

CancerVolume 17, Issue 2 p. 176-184 ArticleFree Access Lipid droplets in the cytoplasm of malignant cells Charles A. Apffel M.D., Charles A. Apffel M.D. Research Laboratories, Pondville Hospital, Department of Public Health of the Commonwealth of Massachusetts, P.O. Box 111, Walpole, Mass., and the Bio-Research Institute, Cambridge, Mass.Search for more papers by this authorJohn R. Baker F.R.M.S., John R. Baker F.R.M.S. Research Laboratories, Pondville Hospital, Department of Public Health of the Commonwealth of Massachusetts, P.O. Box 111, Walpole, Mass., and the Bio-Research Institute, Cambridge, Mass.Search for more papers by this author Charles A. Apffel M.D., Charles A. Apffel M.D. Research Laboratories, Pondville Hospital, Department of Public Health of the Commonwealth of Massachusetts, P.O. Box 111, Walpole, Mass., and the Bio-Research Institute, Cambridge, Mass.Search for more papers by this authorJohn R. Baker F.R.M.S., John R. Baker F.R.M.S. Research Laboratories, Pondville Hospital, Department of Public Health of the Commonwealth of Massachusetts, P.O. Box 111, Walpole, Mass., and the Bio-Research Institute, Cambridge, Mass.Search for more papers by this author First published: February 1964 https://doi.org/10.1002/1097-0142(196402)17:2<176::AID-CNCR2820170207>3.0.CO;2-2Citations: 16AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References 1 Baker, J. R.: Histochemical recognition of lipinc. Quart. J. Micr. Sr. 87: 441– 470, 1946. 2 Bessis, M.: Cytology of the Blood and the Blood-Forming Organs. (Transl. by Eric Ponder.) New York, N. Y. Crime & Stratton, Inc. 1956; pp. 491– 492. 3 Dausset, J.: Essai de differenciation des diverses variétés de leucémies aiguës par l'examen du sang et de la moelle à l'état frais. Sang 21: 610– 622, 1950. 4 Dausset, J., and Schwarzman, V.: Influence of age and sex upon frequency and cytologic types of human leukemias; evidence of myeloid: lymphoid antagonism Blood 6: 976– 989, 1951. 5 Ekwall, P.: Solubilization of lipophilic substances by protein-association colloid complexes. In G. Popják, and E. Le Breton, Eds.: Biochemical Problems of Lipids. New York, N. Y. Interscience Publishers, Inc. 1956; pp. 120– 126. 6 Gall, E. A.: Technic and application of supravital staining. J. Lab. & Clin. Med. 20: 1276– 1293, 1935. 7 Gall, E. A.: Previously undescribed granule within lymphocyte. Am. J. M. Sc. 191: 380– 388, 1936. 8 Gey, G. O.; Shapras, P.; Bang, F. B., and Gey, M. K.: Some relations of inclusion droplets (pinocytosis-Lewis) and mitochondrial behavior in normal and malignant cells. In Fine Structure of Cells; Symposium Held at the VIIIth Congress of Cell Biology, Leyden, 1954. New York, N. Y. Interscience Publishers, Inc. 1955; pp. 38– 54. 9 Hempelmann, L. H., and Knowlton, N. P., Jr.: Nature of neutral red staining refractive particles in lymphocytes of blood of normal humans. Blood 8: 524– 535, 1953. 10 King, T. J., and Briggs, R.: Changes in nuclei of differentiating gastrula cells, as demonstrated by nuclear transplantation. Proc. Nat. Acad. Sc. 41: 321– 325, 1955. 11 Kosenow, W.: Lebende Blutzellen im Fluoreszenz- und Phasenkontrastmikroskop; experimentelle Prüfungen und vergleichende cytomorphologische Untersuchungen zur Anwendung der supravitalen Fluorochromierung und des Phasenkontrastverfahrens auf Strukturprobleme der Hämatologie. Acta haemat. suppl. 4: 1– 288, 1956. 12 Nöller, H. G.: Phasenkontrastmikroskopische Beobachtungen am Blute bei Hepatitis epidemica. Ärztl. Forsch. 6: 185– 188, 1952. 13 Novikoff, A. B.: Transplantable rat liver tumor induced by 4-dimethylaminoazobenzene. Cancer Res. 17: 1010– 1027, 1957. 14 Novikoff, A. B.: Approaches to in vivo function of subcellular particles. In T. Hayashi, Ed.: Subcellular Particles. New York, N. Y. The Ronald Press Company. 1959; pp. 1– 22. 15 Novikoff, A. B.: Intracellular localization of chemical constituents. In R. C. Mellors, Ed.: Analytical Cvtology; Methods for Studying Cellular Form and Function, 2d ed. New York, N. Y. McGraw-Hill Book Company. 1959; pp. 69– 168. 16 Novikoff, A. B.: Enzyme localization in tumor cells. In Cell Physiology of Neoplasia; a Collection of Papers Presented at the Fourteenth Annual Symposium on Fundamental Cancer Research, 1960. Austin, Texas. University of Texas Press. 1960; pp. 219– 268. Citing Literature Volume17, Issue2February 1964Pages 176-184 ReferencesRelatedInformation