Association of CMV-specific T-cell immunity and risk of CMV infection in lung transplant recipients.

BACKGROUND: Protecting against CMV infection and maintaining CMV in latent state are largely provided by CMV-specific T-cells in lung transplant recipients. The aim of the study was to assess whether a specific T-cell response is associated with the risk for CMV infection in seronegative patients who are at high risk for delayed CMV infection. METHODS: All CMV-seronegative recipients (R-) from CMV-seropositive donors (D+) between January 2018 and April 2019 were included and retrospectively screened for CMV infection before and after assessment of CMV-specific cell-mediated immunity. RESULTS: Thirty-one of the 50 patients (62%) developed early-onset CMV infection. Lower absolute neutrophil counts were significantly associated with early-onset CMV infection. Antiviral prophylaxis was ceased after 137.2 ± 42.8 days. CMV-CMI were measured at a median of 5.5 months after LTx. 19 patients experienced early and late-onset CMV infection after prophylaxis withdrawal within 15 months post transplantation. Positive CMV-CMI was significantly associated with lower risk of late-onset CMV infection after transplantation in logistic and cox-regression analysis (OR=0.05, p = .01; OR=2,369, p = .026). CONCLUSION: D+/R- lung transplant recipients are at high risk of developing early and late-onset CMV infection. Measurement of CMV-CMI soon after transplantation might further define the CMV infection prediction risk in LTx recipients being at high risk for CMV viremia.

Expression of different carbohydrate tumour markers and galectins 1 and 3 in normal squamous and malignant epithelia of the upper aaerodigestive tract.

AIM: Tumour markers hold a great relevance in the diagnosis and the follow-up treatment of different kinds of human carcinoma. Although head and neck cancer occurs frequently, there is still lack of appropriate tumour markers. Our investigation on the expression of sialyl Lewis A (CA19-9) in laryngeal carcinomas, consists of systematical analysis of oncofetal carbohydrates and of galectins 1 and 3 in different normal and malignant tissues of the aerodigestive tract. MATERIALS AND METHODS: Paraffin-embedded sections of normal tongue, vocal cord, larynx, pharynx and epiglottis, representing normal control tissue and laryngeal cancer tissue were incubated with monoclonal antibodies against sialyl Lewis A and X (sLeA and X), Lewis Y (LeY), the Thomsen-Friedenreich (TF) antigen and galectin 1 and 3 (Gal-1 and -3). A staining reaction was carried out with ABC-peroxidase and diaminobenzidine (DAB). Tissue of breast cancer was used as a positive control. Mouse IgM, as isotype control antibody, was used as a negative control. Semi quantitative evaluation was carried out double-blinded, by two independent investigators, including a pathologist. RESULTS: Squamous epithelia of all investigated normal tissues of the aerodigestive tract show nearly the same pattern. Most impressive findings are the very weak expression of Gal-1 and the total absence of the TF antigen. Laryngeal cancer reveals high amounts of sLeA, Gal-1 and the TF antigen. CONCLUSION: On the basis of our findings in normal tissue of the aeradigestive tract, these three markers qualified as potential tumour markers for carcinoma of the aerodigestive tract. In particular, the high expression of TF in cancer tissue and its absence from the normal tissue is promising for its establishment as a new tumour marker in this field.

Inhibin-betaC subunit expression in normal and pathological human placental tissues.

Inhibins and activins are important regulators of the female reproductive system. Recently, a novel inhibin betaC subunit has been identified. However, only limited data on the expression of this novel inhibin-betaC subunit in normal and pathological human placentas exist. Tissue specimens of normal, preeclamptic, hemolysis, elevated liver enzymes, low platelets (HELLP), and intrauterine growth restriction (IUGR) pregnancies (n=24) were obtained at the conclusion of a cesarean section. Normal and pathological placental tissues were analyzed by an immunohistochemical staining reaction with a specific antibody against this novel inhibin-betaC subunit. Overall, expression of the inhibin-betaC subunit could be demonstrated in normal and pathological placental tissue. The immunoreactive score (IRS) for inhibin-betaC did not show any significant differences between normal, preeclamptic, HELLP, and IUGR tissue in extravillous trophoblast and syncytiotrophoblast cells. Immunolabelling of this novel inhibin-ßC protein in normal and pathological placental tissue was demonstrated, although no differences in the staining intensity could be observed. Therefore, the inhibin-ßC isoform might not primarily be involved in the pathogenesis of these pregnancy-associated disorders. The functional role of this novel inhibin-betaC subunit in normal and pathological human placenta is still quite unclear and should thus be further investigated.

Immunolabelling of the inhibin/activin-ßC subunit in normal and malignant human uterine cervical tissue and cervical cancer cell lines.

Inhibins are dimeric glycoproteins, composed of an α-subunit and one of two possible ß-subunits (ßA or ßB), with substantial roles in human reproduction and in endocrine-responsive tumours. Recently a novel ß subunit named ßC was described, although it is still unclear if normal or cancerous cervical epithelial cells as well as cervical cancer cell lines can synthesise the inhibin-ßC subunit. Four normal cervical tissue samples together with specimens of well-differentiated squamous cervical cancer and adenocarcinoma of the cervix were immunohistochemically analyzed. Additionally, two cervical carcinoma cell lines (HeLa and CaSKi) were analyzed by immunofluorescence for the expression of this novel subunit. We demonstrated for the first time an immunolabelling of the inhibin-ßC subunit in normal and malignant cervical tissue, as well as cervical cancer cells. Although the physiological role is still unclear in cervical tissue, the inhibin-ßC subunit might play important roles in carcinogenesis. Moreover, the synthesis of this subunit in cervical carcinoma cell lines of squamous and epithelial origins allows the use of these cell lines in elucidating its functions in cervical pathogenesis.

Inhibin/activin-betaC subunit does not represent a prognostic parameter in human endometrial cancer.

INTRODUCTION: Inhibins, dimeric peptide hormones composed of an α subunit and one of two possible ß subunits (betaA or betaB), exhibit substantial roles in human reproduction and in endocrine-responsive tumors. Recently, two novel inhibin-beta subunits, defined as betaC and betaE, have been identified in humans. However, the prognostic significance and clinical implications of the novel inhibin-betaC subunit in endometrial cancers is still quite unclear. MATERIALS AND METHODS: A series of 296 uterine endometrial carcinomas were immunohistochemically analyzed with specific antibody against the inhibin-betaC subunit. The staining reactions were correlated with several clinicopathological characteristics and the clinical outcome. RESULTS: Endometrial cancer tissue demonstrated an immunolabelling against the inhibin-betaC subunit. The inhibin-betaC expression in endometrial carcinoma samples revealed a significant association with hemangiosis. However, the expression of this inhibin subunit did not affect patients' progression-free, cause-specific and overall survival. CONCLUSION: Overall, inhibin-betaC subunit was demonstrated in endometrial cancer tissue. This novel betaC subunit demonstrated a significant association with hemangiosis although without any impact on the patients' survival. Moreover, the inhibin-betaC subunits did not constitute an independent prognostic parameter in endometrial cancer patients. Therefore, the isolated analysis of this subunit might be of minor prognostic value in identifying high-risk patients.

Evidence of inhibin/activin subunit betaC and betaE synthesis in normal human endometrial tissue.

BACKGROUND: Inhibins are important regulators of the female reproductive system. Recently, two new inhibin subunits betaC and betaE have been described, although it is unclear if they are synthesized in normal human endometrium. METHODS: Samples of human endometrium were obtained from 82 premenopausal, non-pregnant patients undergoing gynecological surgery for benign diseases. Endometrium samples were classified according to anamnestic and histological dating into proliferative (day 1-14, n = 46), early secretory (day 15-22, n = 18) and late secretory phase (day 23-28, n = 18). Immunohistochemical analyses were performed with specific antibodies against inhibin alpha (n = 81) as well as inhibin betaA (n = 82), betaB (n = 82), betaC (n = 74) and betaE (n = 76) subunits. RT-PCR was performed for all inhibin subunits. Correlation was assessed with the Spearman factor to assess the relationship of inhibin-subunits expression within the different endometrial samples. RESULTS: The novel inhibin betaC and betaE subunits were found in normal human endometrium by immunohistochemical and molecular techniques. Inhibin alpha, betaA, betaB and betaE subunits showed a circadian expression pattern, being more abundant during the late secretory phase than during the proliferative phase. Additionally, a significant correlation between inhibin alpha and all inhibin beta subunits was observed. CONCLUSIONS: The differential expression pattern of the betaC- and betaE-subunits in normal human endometrial tissue suggests that they function in endometrial maturation and blastocyst implantation. However, the precise role of these novel inhibin/activin subunits in human endometrium is unclear and warrants further investigation.

Inhibin/activin-betaC subunit in human endometrial adenocarcinomas and HEC-1a adenocarcinoma cell line.

INTRODUCTION: Inhibins and activins are important regulators of the female reproductive system. Recently, two novel inhibin subunits, named betaC (ßC) and betaE (ßE), have been identified. However, only limited data on the expression of the ßC subunit in human endometrioid adenocarcinomas exist. MATERIALS AND METHODS: Samples of uterine endometrioid adenocarcinomas were obtained and analysed by immunohistochemistry for the immunolabelling with an inhibin-ßC antibody. Additionally, the endometrial cancer cell line HEC-1a was used to assess the inhibin-betaC expression with the use of immunofluorescence. RESULTS: Expression of the inhibin-ßC subunit was demonstrated at the protein level by means of immunohistochemical evaluation in human endometrioid adenocarcinomas and the HEC-1a cell line. DISCUSSION: This study demonstrated, for the first time, that the novel inhibin/activin-ßC subunit is expressed in human endometrioid adenocarcinomas and in the human endometrial carcinoma cell line HEC-1a. Whether this novel ß-subunit has a substantial role in the pathogenesis and malignant transformation in human endometrium is still under investigation.

The metastasis-associated gene MTA3 is downregulated in advanced endometrioid adenocarcinomas.

The metastasis-associated gene MTA3 has an important function in invasion and metastasis of human cancer cells. Therefore, the aim of this study was to investigate the expression of this protein in endometrial adenocarcinomas and to analyse potential correlations between this nuclear transcription factor and estrogen receptors in endometrial adenocarcinomas. Additionally, we evaluated whether MTA3 might be a prognostic parameter in endometrioid adenocarcinomas. Endometrioid adenocarcinomas were obtained from 200 patients and immunohistochemically analysed for MTA3 and estrogen receptor alpha and beta (ER-alpha and ER-beta) expression. Overall, endometrioid adeno-carcinomas of histological differentiation grade 3 demonstrated a significantly lower expression of MTA3 compared to carcinomas of histological grade 1 and 2 (p<0.05). MTA3 expression is reduced in endometrioid adenocarcinomas of poor differentiation, though without any correlation to ER-alpha and ER-beta expression. Furthermore, the expression of MTA3 did not affect progression-free, cause-specific and overall survival. Overall, MTA3 did not constitute an independent prognostic factor in this study, suggesting that MTA3 is not a useful marker to assess and identify high-risk patients with endometrial adenocarcinomas. Still, the downregulation of MTA3 predispose this cell type to be of high metastatic potential after malignant transformation, playing an essential, but as yet unknown role in human endometrial carcinogenesis.

Determination of glycodelin-A expression correlated to grading and staging in ovarian carcinoma tissue.

BACKGROUND: Glycodelin is a glycoprotein with a molecular weight of 28 kDa. Due to its different glycosylation, several glycodelin molecules have been described, including glycodelin-A (amniotic fluid). The precise function of glycodelin is still not well understood, although immunosuppressive, contraceptive and marker of morphological differentiation roles have been demonstrated. The aim of this study was to assess the expression of glycodelin in malignant tumors of the ovary correlated to grading and staging. MATERIALS AND METHODS: Paraffin sections of 187 ovarian cancer specimens (including 132 serous, 22 endometrioid, 17 mucinous, 12 clear cell and 4 borderline tumors) were analyzed with a monoclonal antibody GdA (MAb) and a peptide polyclonal antibody (PAb) against glycodelin. The intensity and distribution of the specific immunohistochemical staining reaction was evaluated by using a semi-quantitative method (immunoreactive score (IRS)). RESULTS: We identified significant changes in glycodelin-A expression corresponding to grading and staging. Analysis of glycodelin expression with the PAb did not result in significant differences. Glycodelin-A staining was significantly reduced in G2 carcinomas compared to G1 ovarian cancer tissue. Moreover, ovarian cancer of surgical stage FIGO III-IV demonstrated a significant lower glycodelin-A expression compared to FIGO I-II stage tumors. CONCLUSION: Glycodelin is a glycoprotein with immunosuppressive function. In particular, serous and endometrioid tumor tissue showed strong glycodelin-A expression. In addition, glycodelin expression is reduced in G2 and FIGO III-IV stages. Therefore, glycodelin also seems to be an important marker of morphological differentiation in ovarian cancer. The use of glycodelin as a tumor marker in ovarian carcinomas is currently under investigation.

Expression of the carbohydrate tumor marker Sialyl Lewis a (Ca19-9) in squamous cell carcinoma of the larynx.

BACKGROUND: The clinical relevance of the carbohydrate antigen Sialyl Lewis a (SLea) as a serum tumor marker in diagnosis and follow-up treatment is unquestioned in a broad spectra of human carcinomas. Overexpression of this antigen is combined with poor prognosis and malignant relapse. The aim of our study was the systematic investigation of SLea expression in squamous cell carcinoma of the larynx versus normal and phlogistic tissue. MATERIALS AND METHODS: Paraffin-embedded sections of normal, phlogistic and squamous cell carcinoma tissue were incubated with a monoclonal antibody against SLea. The staining reaction was performed using ABC-Peroxidase and DAB. As a positive control tissue of breast cancer was used and the negative control was performed with unspecific mouse IgM. Semiquantitative evaluations were carried out double-blinded by two independent investigators, including a pathologist. RESULTS: A very faint expression of SLea (Ca19-9) in normal laryngeal tissue, a moderate upregulation in phlogistic tissue and a dramatic upregulation in some types of squamous cell carcinoma of the larynx were observed. Laryngeal cancer is the most common cancer of the upper aerodigestive tract. Most cases of laryngeal cancer are squamous cell carcinoma and can be classified into: well differentiated (more than 75% keratinization), moderately differentiated (25-75% keratinization), and poorly differentiated (<25% keratinisation) carcinomas. CONCLUSION: The results of this study indicate that SLea is a potential tumor marker in carcinoma of the larynx.

Immunolabeling of the inhibin-ßA and -ßB subunit in normal and malignant human cervical tissue and cervical cancer cell lines.

OBJECTIVES: Inhibins, dimeric peptide hormones composed of an α-subunit and 1 of 2 possible ß subunits (ßA or ßB), exhibit substantial roles in human reproduction and in endocrine-responsive tumors. However, it is still unclear whether normal and cancerous cervical tissues as well as cervical cancer cell lines express the inhibin-ßA and -ßB subunits. MATERIALS AND METHODS: Normal human uterine cervical tissue was obtained from 4 premenopausal nonpregnant patients. In addition, a total of 32 specimens of cervical intraepithelial neoplasia (CIN) of different stages were obtained (CIN 1 = 10, CIN 2 = 9, and CIN 3 = 13). Moreover, 30 squamous cervical cancer samples of well-differentiated (grade 1; n = 10), moderate differentiated (grade 2; n = 10), and poorly differentiated (grade 3; n = 10) grading were analyzed. RESULTS: An immunohistochemical staining reaction for inhibin-ßA and -ßB subunits could be observed in normal and malignant cervical tissue as well as in cervical cancer cell lines. Regarding inhibin-ßA significant differences were observed between normal tissue and CIN 1 and CIN 3. Moreover, the immunohistochemical staining reaction for inhibin-ßA was significantly higher in CIN 3 compared with that in cervical carcinoma grades 1 and 2. The inhibin-ßB expression was higher in CIN and cervical cancer compared with that in normal cervical tissue. Inhibin-ßB was significantly higher in CIN 2 and CIN 3 compared with cancer tissues of histological grade 1. In addition, a significant increase of the staining intensity was observed between cervical cancer grades 1 and 2 as well as grade 3. CONCLUSIONS: Both inhibin-ß subunits demonstrated a differential expression in CIN and squamous cancer, suggesting important roles in cervical carcinogenesis. Inhibin-ßA might be important during progression of CIN, whereas the inhibin-ßB subunit could exert a substantial function during differentiation of cervical carcinomas. Moreover, the synthesis of this subunit in cervical carcinoma cell lines also allows the use of this cell line to elucidates their functions in cervical cancer pathogenesis.

Peroxisome proliferator-activated receptor-gamma in normal human pregnancy and miscarriage.

Peroxisome proliferator-activated receptors (PPAR) belong to the superfamily of nuclear hormone receptors. Recent investigations emphasize a possible involvement of PPAR in obstetric and gynaecologic disorders like polycystic ovarian syndrome, endometriosis and preeclampsia. The aim of this study was to determine the frequency and distribution of peroxisome proliferator-activated receptor-gamma (PPARgamma) in normal human pregnancy and miscarriage. Placental tissue was obtained from normal human pregnancy and miscarriage during the first trimester of pregnancy. PPARgamma localisation was investigated by immunohistochemical methods. Immediate immunoreactivity of PPARgamma was observed in villous and extravillous trophoblast nuclei in normal first trimester pregnancy. A significantly enhanced labelling of PPARgamma was identified in extravillous trophoblast of miscarriage patients. This enhanced immunopositivity was also found in nuclei of villous trophoblast cells of miscarriage patients but without statistical significance. Because trophoblast invasion is negatively correlated to PPARgamma stimulation and blocking of PPARgamma leads to increased trophoblast invasion, our findings may suggest that enhanced expression of PPARgamma in abortive extravillous trophoblasts may be one factor linked to miscarriage.

Inhibin-alpha subunit is an independent prognostic parameter in human endometrial carcinomas: analysis of inhibin/activin-alpha, -betaA and -betaB subunits in 302 cases.

Inhibins are dimeric glycoproteins, composed of an alpha-subunit (inhibin-alpha) and one of two possible beta-subunits (betaA or betaB), with substantial roles in human reproduction and in endocrine-responsive tumours. The aims of this study were to determine the distribution of inhibin-alpha, -betaA and -betaB subunits in malignant human endometrial tissue and the assessment of an association with specific clinicopathologic tumour features and clinical outcome. A series of 302 endometrial cancer tissue samples were immunohistochemically analysed with monoclonal antibodies against inhibin subunits. The inhibin-alpha subunit showed a significant association with histological grading, surgical staging, lymph node status and diabetes in patients with endometrial cancer. Interestingly, loss of inhibin-alpha expression resulted in a poorer survival of endometrial cancer patients. Additionally, survival analysis demonstrated that inhibin-alpha immunoreactivity was an independent prognostic factor for progression-free survival, cause-specific survival as well as for overall survival. In contrast, although inhibin-betaA- and -betaB subunits showed a significant association between endometrial histological subtypes and histological grading, both subunits were not found to be associated with survival in endometrial cancer patients. Therefore, inhibin-alpha immunostaining might be used as a simple and efficient marker to identify high-risk patients leading to the selection of patients for an aggressive adjuvant therapy.

Leptin and peroxisome proliferator-activated receptors: impact on normal and disturbed first trimester human pregnancy.

Recent in vitro and in vivo studies emphasize the impact of leptin, peroxisome proliferator-activated receptors (PPAR) and PPAR coactivators (retinoic X receptor a (RXR), amplified in breast cancer-3 gene (AIB3)) on placental and fetal development. Therefore, the frequency and distribution pattern of PPAR, RXR, AIB3 and leptin expression in normal human first trimester pregnancy, miscarriage and hydatidiform mole was investigated by immunohistochemistry and double immunofluorescence staining. Enhanced expression of PPAbeta/delta, RXR and AIB3 was identified in miscarried placentas. With regard to hydatidiform mole, increased expression of PPARgamma and PPARbeta/delta was observed, whereas RXR was significantly down-regulated. Leptin expression was lowest in miscarriage and highest in mole pregnancies. In contrast to trophoblast tissue, expression of leptin in glandular epithelial cells of the decidua was increased in miscarriage. PPAR and leptin expressing cells at the feto-maternal interface were identified as extravillous trophoblast (EVT) by double immunofluorescence and CK7 staining. In summary, significantly reduced leptin expression was accompanied by enhanced PPARbeta/delta, RXR and AIB3 expression in miscarried placentas. However, in mole pregnancy, up-regulation of leptin and increased expression of PPAR was detected. RXR, on the other hand, was down-regulated in mole decidua. So far, the study results implicate strong regulatory interaction of PPARs, their coactivators and leptin in human placentas. PPAR and leptin are potential targets for new treatment strategies concerning pregnancy disorders, such as miscarriage. The increasing knowledge about the role of PPARs and leptin in normal and disturbed pregnancy may help to improve pregnancy outcome.

Erythropoietin and erythropoietin receptor expression in normal and disturbed pregnancy.

OBJECTIVE: Erythropoietin (Epo) is known to regulate the number of circulating erythrocytes. Epo receptor (Epo-R) expression is limited to few organs including the uterus. We investigated differences in Epo and Epo-R expression in normal and disturbed first trimester human pregnancy. STUDY DESIGN: Placental tissue was obtained from normal human pregnancy, abortion and hydatidiform mole during the first trimester of pregnancy. Epo and Epo-R expression was investigated by Immunohistochemistry and real time PCR (TaqMan). The intensity and distribution patterns of Epo and Epo-R expression were evaluated by using a semi-quantitative method (immunoreactive score) as previously described. RESULTS: Epo-R expression was upregulated in the villous trophoblast (VT) of abortive tissue (p=0.002) as compared to normal pregnancy. This was further confirmed on mRNA level. With regard to mole pregnancy, Epo-R expression was also significantly increased in the VT (p<0.001). In extravillous trophoblasts (EVT), only Epo, not Epo-R expression was significantly increased in abortive tissue (p=0.006) as well as in hydatidiform mole (p=0.041) in comparison to normal pregnancy. Identification of EVT as Epo-and Epo-R-positive cells was obtained by double immunofluorescence with CK7 and Epo/ Epo-R double staining. Both mole pregnancy and abortion were accompanied by an upregulation of Epo (p=0.041; p=0.018) and Epo-R expression (p=0.007; p=0.015) in decidual tissue as compared to normal pregnancy. CONCLUSION: Within our study we were able to demonstrate increased expression of Epo and Epo-R in abortive tissue and hydatidiform mole. Whether upregulation of Epo and Epo-R is secondary to placental hypoxia as part of the abortion process or a risk factor of its own, needs to be further investigated.

New derivatives of vitamin B12 show preferential targeting of tumors.

Rapidly growing cells show an increased demand for nutrients and vitamins. The objective of our work is to exploit the supply route of vitamin B12 to deliver new derivatives of this vital vitamin to hyperproliferative cells. To date, radiolabeled ((57)Co and (111)In) vitamin B12 derivatives showed labeling of tumor tissue but also undesired high accumulation of radioactivity in normal tissue. By abolishing the interaction of a tailored vitamin B12 derivative to its transport protein transcobalamin II and therefore interrupting transcobalamin II receptor and megalin mediated uptake in normal tissue, preferential accumulation of a radiolabeled vitamin in cancer tissue could be accomplished. We identified transcobalamin I on tumors as a possible new receptor for this preferential accumulation of vitamin-mediated targeting. The low systemic distribution of radioactivity and the high tumor to blood ratio opens the possibility of a more successful clinical application of vitamin B12 for imaging or therapy.

Prognostic significance of oestrogen receptor alpha (ERalpha) and beta (ERbeta), progesterone receptor A (PR-A) and B (PR-B) in endometrial carcinomas.

The expression of the classic steroid receptors ERalpha and PR-A has been correlated with stage, histological grade and survival in endometrial cancer. Endometrial cancer samples (293) were immunohistochemically analysed with monoclonal antibodies against the four steroid receptors. The loss of ERalpha, PR-A and PR-B resulted in a poorer survival in endometrial cancer patients, while ERbeta expression did not demonstrate any correlations with several analysed clinicopathological characteristics and did not affect survival. Additionally, multivariate survival analysis demonstrated that PR-B was a significant independent prognostic factor for cause-specific survival. In contrast, although ERalpha and PR-A showed a significant association between different endometrial histological subtypes and grading, both receptors were not independent factors with survival in endometrial carcinoma patients. Therefore, the PR-B immunostaining might be used as an easy, simple and highly efficient marker to identify high-risk patients and may aid in the selection of patients for a more aggressive adjuvant therapy.

Mucin 1, Thomsen-Friedenreich expression and galectin-1 binding in endometrioid adenocarcinoma: an immunohistochemical analysis.

BACKGROUND AND AIM: Altered mucin 1 (MUC1) secretion patterns have been implicated in several cancerous conditions including gastric, colorectal and breast carcinomas. Additionally, an association between the expression of MUC1, Thomsen-Friedenreich (TF) antigen, and binding of gal-1 (gal-1) has been proposed. Therefore, the aims of this study were to determine the frequency and tissue distribution of MUC1, TF and gal-1 binding in endometrioid adenocarcinomas. MATERIALS AND METHODS: Endometrial carcinomas diagnosed with only one histological tumor form (endometrioid adenocarcinomas) were obtained from 70 patients and classified according to the WHO grading system (G1 = 50; G2 = 12; G3 = 8). An immunohistochemical analysis was performed with specific antibodies against MUC1 and TF and in addition with biotinylated gal-1, followed by a semiquantitative evaluation and statistical analysis (chi2 test and Spearman's correlation coefficient). RESULTS: MUC1, TF and gal-1 were observed in human endometrioid adenocarcinomas. The MUC1 and gal-1 immunoreaction increased from G1 to G3, while TF demonstrated a lower intensity in G3 compared to G1, although with no statistical significance. However TF showed a significant correlation with MUC1 (p = 0.019) in G1 and G2 endometrioid adeno-carcinomas, with no observed correlation in G3 tumors. MUC1 and TF demonstrated a significant (p = 0.006 and p = 0.046, respectively) down-regulation in surgically staged FIGO III/IV compared to FIGO I/II. Gal-1 binding was up-regulated in FIGO III/IV although with no statistical significance. Interestingly, there was an association between gal-1 binding and lymphangiosis (p = 0.008). CONCLUSION: An immuno-histochemical expression of MUC1 and TF and gal-1 binding was demonstrated in human endometrioid adenocarcinomas. Although no significant expression patterns could be demonstrated within different nuclear grading, TF and MUC1 showed a significant correlation in G1/G2 tumors. Therefore, MUC1 and TF might be associated with endometrial malignant transformation. Additionally, MUC1 and TF were down-regulated in stage III/IV tumors, while a higher binding of gal-1 was observed in stage III/IV tumors, suggesting a substantial role of this antigen in endometrial carcinogenesis. Gal-1 binding was associated with lymphangiosis, which is thought to be a poor prognostic marker in endometrial adenocarcinomas. Therefore, MUC1, TF and galectin might have important roles in endometrial pathogenesis and malignant transformation. However, their utilization as specific tumor markers remains unclear and further studies are warranted.

Expression of HPV, steroid receptors (ERalpha, ERbeta, PR-A and PR-B) and inhibin/activin subunits (alpha, betaA and betaB) in adenosquamous endometrial carcinoma.

AIM: The aim of the study was to determine possible pathogenetic factors and molecules which may be used as tumor markers of adenosquamous endometrial carcinoma. MATERIALS AND METHODS: Eight adenosquamous endometrial carcinomas were immunohistochemically tested with specific monoclonal antibodies for HPV (polyclonal anti-HPV and monoclonal anti-HPV 18), estrogen receptors ER-alpha and ER-beta, progesterone receptors PR-A and PR-B and the inhibin/activin subunits inhibin-alpha, -betaA and -betaB. RESULTS: HPV 18 and the polyclonal HPV antibody was detected in all adenosquamous endometrial carcinomas, both in the endometrioid (n = 7/8) and squamous (n = 8/8) parts of the tumor. Neither ER-alpha or ER-beta were detectable in any tumor, in contrast to PR-A and PR-B which were detected in about half of these tumors (PR-A: n = 5/8 and PR-B: n = 2/8). Inhibin-alpha and -betaB were not detected, while inhibin-betaA was expressed in all adenosquamous carcinomas. CONCLUSION: The carcinogenesis of adenosquamous endometrial carcinomas was associated with HPV infection. Adenosquamous endometrial carcinomas seem not to be controlled by estrogens. The absence of the expression of the inhibin-alpha subunit suggests a tumor-suppressive function in adenosquamous endometrial tumors. The absence of the expression of the inhibin-betaB subunit, which is probably a marker of differentiation, points to the malignancy of these tumors. The other inhibin subunit, inhibin-betaA, was expressed in all adenosquamous tumors. It remains to be clarified if these parameters can be used as tumor markers.

Immunohistochemical visualisation of cathepsin-D expression in breast cancer.

BACKGROUND: Cathepsin D (Cath-D), a lysosomal protease, is considered to be involved in the breakdown of the extracellular matrix during the process of tumour metastasis. Its expression in breast cancer in association with known factors of prognosis was investigated in this study. MATERIAL AND METHODS: 120 breast cancer tumours were analysed immunohistochemically and evaluated with the immunoreactive score (IRS). Statistical evaluation was performed using the Mann-Whitney test (p < 0.05). RESULTS: For nodal-positive tumors we found a statistically significant increase of Cath-D immunohistochemical reaction. Ductal carcinomas showed a significantly higher immunohistochemical reaction compared to lobular carcinomas. We found a non-significant increase from G1 to G2 and G1 to G3, and a non-significant increase of Cath-D expression of all receptor-positive over all receptor-negative tumours. CONCLUSION: Cath-D expression was found to be associated with known prognostic factors. The clinical relevance of the observed difference depending on the histological type needs further investigation. Cath-D might be a useful marker to discriminate between ductal and lobular subtypes of breast cancer.