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Secreted mucins constitute a crucial part of the gel that protects respiratory and digestive epithelia, being MUC2/Muc2 the predominant gel-forming mucin of the intestine while MUC5AC/Muc5ac is one of the gel-forming mucins most expressed at the airways. In this study, we have analyzed Muc2 and Muc5ac during rat development by using immunohistochemistry, Western blotting and RT-PCR. We demonstrated that rat Muc2 was expressed in fetal intestinal goblet cells of surface epithelium of villi and developing Lieberkühn crypts. In neonates and adults, Muc2 was expressed at luminal goblet cells of small and large intestine and at gastric mucous and glandular cells. Muc5ac protein was observed in embryonic gastric and lung samples; expression increased during development and postnatal and adult life. After birth, a low reaction was detected at the tracheal surface epithelium and glands, which increased in adults. Fil: Ferretti, Valeria. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Segal Eiras, Amada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina Fil: Barbeito, Claudio Gustavo. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Croce, María Virginia. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina

Breast cancer spreading to different organs have been related to different molecules and mechanisms, but cutaneous metastasis remains unexplored. Increasing evidence showed that MUC1 and some of its carbohydrate associated antigens may be implicated in breast cancer metastasis. In this study we analyzed these tumor markers in order to identify breast cancer cutaneous metastatic profiles. A cohort of 26 primary tumors from breast cancer patients with cutaneous metastases were included; also, cutaneous and lymphatic node metastatic samples and primary tumors from breast cancer patients without metastases were analysed. Immunohistochemical (IHC) studies demonstrated that both underglycosylated MUC1 (uMUC1) and sialyl Lewis x (sLex) to be positively associated with cutaneous metastatic primary tumors (p 0.05). Notably, a high percentage of tumors with cutaneous metastases were characterized as triple negative and Her2+ tumors (37.5 % and 29 %, respectively). Some discordant results were found between primary tumors and their matched cutaneous metastases. To determine if MUC1 variants may be carriers of carbohydrate antigens, subcellular fractions from a cutaneous metastatic lesion were obtained, immunoprecipitated and analyzed by Western blot. We found that the isolated uMUC1 with a molecular weight of200 kDa was also the site for binding of anti-sLex MAb; in coincidence, a high correlation of positive IHC expression of both markers was observed. Our findings confirm that breast cancer cutaneous metastases were associated to highly malignant primary tumors and sustain the hypothesis that u-MUC1 and sLe x may drive breast cancer cutaneous metastases.

Aim Colorectal cancer (CRC) is one of the most prevalent malignancies in Argentina with 11,043 new cases and 6,596 deaths estimated to have occurred in 2008. The present study was developed to clarify the differential expression of MUC1, MUC2, sLex, and sLea in colorectal cancer patients and their relationship with survival and clinical and histological features. Methods Ninety primary tumor samples and 43 metastatic lymph nodes from CRC patients were studied; follow-up was documented. Twenty-six adenoma and 68 histological normal mucosa specimens were analyzed. An immunohistochemical approach was applied and statistical analysis was performed. Results In tumor samples, MUC1, sLea, and sLex were highly expressed (94%, 67%, and 91%, respectively); also, we found a significantly increased expression of the 3 antigens in primary tumors and metastatic lymph nodes compared with normal mucosa and adenomas. MUC2 was expressed in 52% of both normal mucosa and CRC samples; this reactivity significantly decreased in metastatic lymph nodes (pConclusions The correlation of sLex overexpression in primary tumors and metastatic lymph nodes, the discrimination among the normal, adenoma, and CRC groups based on sLex expression, as well as its association with recurrence and survival, all suggest a prognostic role of sLex in Argentinian CRC patients.

The aim of this study was to elucidate whether the IgG humoral immune response to breast cancer cells is directed to the aberrant mucin-1 (MUC1) associated to this type of cancer. To this aim, an adaptation of immunohistochemistry (IHC) was performed on samples of 45 breast cancer tissues, 12 benign disease tissues, and 31 normal tissues, incubated with matched serum samples from the same patients. Each serum sample was also incubated, with a modified immunocytochemistry (ICC), with MCF7 cells. In both techniques, serum was employed instead of the primary antibody. In the case of IHC, the reactivity with sera diminished when added after previous incubation of the tumor/tissue with an anti-MUC1 mAb; the reduction in reactivity was: from 93% to 44% in breast cancer tissues, and from 100% to 67% in benign disease tissues. The reactivity of normal samples (36%) remained unchanged. In the case of ICC, the reactivity with sera decreased after incubation with anti-MUC1 mAb from 71% to 16% in breast cancer tissues, from 83% to 0% in benign disease tissues, and from 52% to 10% in normal serum samples. These results were confirmed employing siRNA MUC1 transient gene knockdown. By Western blot analysis – after immunoprecipitation (IP) of the circulating MUC1– and ELISA, the TF antigen was detected in circulating MUC1 in all breast cancer and benign samples while Tn was detected in 38% of the samples. The existence of IgG autoantibodies against aberrantly glycosylated MUC1 may have a protective role and may contribute to a better prognosis in some patients. Enhancement of this natural immune response may constitute an alternative therapeutic strategy.

In Argentina, there are no studies evaluating neither breast cancer screening nor risk and prognostic factors in relation to socioeconomic status among women in metropolitan areas. Taking into account that Argentina presents social and economical disparities and that there is a mixture of features of both developed and developing societies, it is interesting to compare prognostic and risk factors in disadvantaged and advantaged women as it would clarify the influence of socioeconomic factors in breast cancer biology. The purpose of this study was to compare risk and prognostic factors of invasive breast cancer in two different Argentine populations. Study participants and data collection. A total of 625 women who had a histologically confirmed diagnosis of invasive primary breast cancer were included; 270 patients belonged to a private clinic of the city of La Plata (province of Buenos Aires) belonging to an Advantaged Population (AP) and 355 patients belonged to a public hospital of the city of Neuquén (province of Neuquén, Patagonia) belonging to a Disadvantaged Population (DP). Women of these geographical regions and first diagnosed with invasive primary breast carcinoma from 2002 until 2007 were eligible as cases. There were no racial or ethnic differences between the two groups of women; all of them were born in Argentina. Risk factors included age at diagnosis, menarche and menopause status, breastfeeding and parity, while prognostic factors were: disease stage, number of metastatic lymph nodes, tumor size, histological and nuclear grade, vascular invasion, ER, PR, and Her2neu statuses. Methods: Statistical analysis included frequency analysis and ANOVA (p < 0.05). Results: A remarkable difference between the two populations was found: the age at diagnosis was significantly lower in DP than in AP: 63% of DP versus 44% of AP was Conclusions: Patients belonging to these two different geographical regions constitute two different populations. Breastfeeding and number of children, considered in relation to socio-economic features, are important risk factors of invasive breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-07-13.

The aim was to compare the expression of MUC1 and carbohydrate antigens in 124 tissue samples; 42 fibroadenoma (FA), 23 nonproliferative benign diseases (NPF), 25 usual epithelial hyperplasia (UEH), 7 atypical ductal hyperplasia (ADH), and 27 breast normal tissues. An immunohistochemical approach was adopted, using the following antibodies: reactive with MUC1 variable number of tandem repeats (C595, HMFG2, and SM3 monoclonal antibodies), anti-MUC1-cytoplasmic tail polyclonal antibody (CT33), and anti-carbohydrate antigens (sialyl Lewis x, Lewis x, Lewis y, Tn, and Thomsen-Friedenreich epitopes). Positive area of reaction, intensity, and pattern of expression were considered. A reactivity index was calculated as intensity (I) x 100+percentage of positive area (A). Statistical analysis comprised frequency analysis, P < 0.05, analysis of variance, and multiple correlation with principal component analysis. All samples expressed MUC1, detected by at least one anti-MUC1 antibody whereas Lewis x was the carbohydrate antigen most frequently found in all groups whereas variable number of tandem repeats MUC1 and Lewis x showed the highest correlation: 93% of normal samples, 62.5% of NPF, 87% of FA, 85% of UEH, and finally 80% of ADH. Although principal component analysis using reactivity indexes explained only 39% of data variability, normal samples appeared grouped and separated from benign breast diseases, which remained spread. Thomsen-Friedenreich was the only antigen that showed an increased tendency for positive expression and intensity from NPF through FA, UEH to ADH, whereas it was not detected in normals. With respect to the pattern of expression, an apical pattern was predominantly found in all the groups.

In the course of breast cancer global gene expression studies, we identified an uncharacterized gene known as RHBDD2 (Rhomboid domain containing 2) to be markedly over-expressed in primary tumors from patients with recurrent disease. In this study, we identified RHBDD2 mRNA and protein expression significantly elevated in breast carcinomas compared with normal breast samples as analyzed by SAGE (n = 46) and immunohistochemistry (n = 213). Interestingly, specimens displaying RHBDD2 over-expression were predominantly advanced stage III breast carcinomas (p = 0.001). Western-blot, RT-PCR and cDNA sequencing analyses allowed us to identify two RHBDD2 alternatively spliced mRNA isoforms expressed in breast cancer cell lines. We further investigated the occurrence and frequency of gene amplification and over-expression affecting RHBDD2 in 131 breast samples. RHBDD2 gene amplification was detected in 21% of 98 invasive breast carcinomas analyzed. However, no RHBDD2 amplification was detected in normal breast tissues (n = 17) or breast benign lesions (n = 16) (p = 0.014). Interestingly, siRNA-mediated silencing of RHBDD2 expression results in a decrease of MCF7 breast cancer cells proliferation compared with the corresponding controls (p = 0.001). In addition, analysis of publicly available gene expression data showed a strong association between high RHBDD2 expression and decreased overall survival (p = 0.0023), relapse-free survival (p = 0.0013), and metastasis-free interval (p = 0.006) in patients with primary ER-negative breast carcinomas. In conclusion, our findings suggest that RHBDD2 over-expression behaves as an indicator of poor prognosis and may play a role facilitating breast cancer progression., Facultad de Ciencias Médicas

Background. In head and neck squamous cell car- cinoma (HNSCC), tumor markers may be helpful to evaluate prognosis accurately as well as to improve therapy selection. Detection of human MUC1 has been widely employed for the evaluation of carcinoma patients. This article aims to study MUC1, Tn, sTn, and Lewis antigenic expression in primary HNSCC, lymph node metastasis, and local recurrences. Methods. We used immunohistochemistry, tissue homogeni- zation and differential centrifugation, isopycnic density gradient centrifugation, sodium dodecyl sulfate-polyacrylamide gel elec- trophoresis, and Western blot. Results. In primary tumors, MUC1 was detected in 80.0% of the samples; sLewis x in 23.2%, Lewis x in 45.6%, and Lewis y in 40.8%. Tn and sTn were found in 4.0% and 6.4% of samples, respectively. In metastatic lymph nodes, MUC1 showed a similar positive reaction as in primary tumors. Lewis y was detected in 20% lymph nodes whereas Lewis x, sLewis x, Tn, and sTn did not show differences. Some recurrences expressed MUC1 and only a few Lewis antigens, whereas Tn and sTn were not detected. Conclusion. In primary HNSCC and metastatic nodes, a high expression of MUC1 and Lewis antigens was detected that diminished in local recurrences. We also found that differenti- ated tumors mainly expressed a linear pattern of MUC1CT and Lewis x. V C 2008 Wiley Periodicals, Inc. Head Neck 30: 647- 657, 2008

An immunohistochemical analysis was employed to determine the expression of carbohydrate antigens associated to mucins in normal epithelia. Tissue samples were obtained as biopsies from normal breast (18), colon (35) and oral cavity mucosa (8). The following carbohydrate epitopes were studied: sialyl-Lewis x, Lewis x, Lewis y, Tn hapten, sialyl-Tn and Thomsen-Friedenreich antigen. Mucins were also studied employing antibodies against MUC1, MUC2, MUC4, MUC5AC, MUC6 and also normal colonic glycolipid. Statistical analysis was performed and Kendall correlations were obtained. Lewis x showed an apical pattern mainly at plasma membrane, although cytoplasmic staining was also found in most samples. TF, Tn and sTn haptens were detected in few specimens, while sLewis x was found in oral mucosa and breast tissue. Also, normal breast expressed MUC1 at a high percentage, whereas MUC4 was observed in a small number of samples. Colon specimens mainly expressed MUC2 and MUC1, while most oral mucosa samples expressed MUC4 and MUC1. A positive correlation between MUC1VNTR and TF epitope (r=0.396) was found in breast samples, while in colon specimens MUC2 and colonic glycolipid versus Lewis x were statistically significantly correlated (r=0.28 and r=0.29, respectively). As a conclusion, a defined carbohydrate epitope expression is not exclusive of normal tissue or a determined localization, and it is possible to assume that different glycoproteins and glycolipids may be carriers of carbohydrate antigens depending on the tissue localization considered.

Some mucin genes have been detected during human embryonic and fetal organ development; however, little is known about mucin expression in epidermal development, neither in humans nor in other species. The present research was developed to explore Muc5ac skin expression during pre-and post-natal rat development. Immunohistochemistry (IHC), Western blotting (WB) and RT-PCR were employed. By IHC, Muc5ac protein was found early in embryonic epidermis from day 13 of gestation until seven days after birth when the surface epidermis became negative and the reaction was restricted to secreting sebum cells. In coincidence with IHC findings, WB analysis showed a band at approximately 200KDa at the same periods of development. Results were also confirmed by RT-PCR. Muc5ac expression in rat embryonic epidermis suggests that Muc5ac may play a protective role in embryonic skin previous to birth which may be replaced by pile covering. To our knowledge, this is the first report that confirmed Muc5ac expression during skin development. and airways epithelia.2 It is common knowledge that normal skin exhibits a rather restricted expression of mucins, and it has been demonstrated that epithelial cells of the normal epidermis do not express sialomucins while Muc5ac expression in cancer epidermal cells is well documented.4,5 On the other hand, little is known about mucin expression in epidermal development, neither in humans nor in other species. However, some mucin genes have been detected during human embryonic and fetal organ development according to differential expression patterns in comparison with adult tissues.3,6 The present research was developed to explore Muc5ac skin expression during preand post-natal rat development., Centro de Investigaciones Inmunológicas Básicas y Aplicadas, Facultad de Ciencias Veterinarias

Metastatic development is a complex, multistage process involving modulation of cell phenotype, cell migration, and dynamic homeotypic as well as heterotypic cell-cell interactions. In breast cancer, MUC1 mucin has been emerging as a key molecule involved in metastasis. MUC1 is a large transmembrane glycoprotein expressed by mammary normal epithelial cells but it is overexpressed and underglycosylated in cancer cells. Cutaneous metastasis is a neoplastic lesion localized at the dermis or subcutaneous cellular tissue, which is not contiguous to the primary tumor, with an overall incidence of 5.3%. The most common tumor to metastasize to the skin is breast cancer with an incidence of 24%. We present a minireview on metastatic dissemination with special emphasis on breast cancer cutaneous metastases and the role that MUC1 plays on it., Sociedad Argentina de Fisiología

Background: The glycoprotein MUC1 is overexpressed and underglycosylated in cancer cells. MUC1 is translated as a single polypeptide that undergoes autocleavage into 2 subunits (the extracellular domain and the cytoplasmic tail), and forms a stable heterodimer at the apical membrane of normal epithelial cells. The MUC1 cytoplasmic tail localizes to the cytoplasm of transformed cells and is targeted to the nucleus. Aims: To study the expression of the MUC1 extracellular subunit in cell nuclei of neoplastic breast, head and neck, and colon samples. Materials and methods: 330 primary tumor samples were analyzed: 166 invasive breast carcinomas, 127 head and neck tumors, and 47 colon tumors; 10 benign breast disease (BBD) and 40 normal specimens were also included. A standard immunohistochemical method with antigen retrieval was performed. Nuclear fractions from tissue homogenates and breast cancer cell lines (ZR-75, MDA-MB-231, MCF7, and T47D) were obtained and analyzed by Western blotting (WB). The anti-MUC1 extracellular subunit monoclonal antibody HMFG1 was used for immunohistochemistry. Results: 37/166 breast cancer specimens, 5/127 head and neck cancer specimens, 2/47 colon cancer samples, and 3/10 BBD samples showed immunohistochemical staining at the nuclear level. No nuclear reaction was detected in normal samples. By WB, breast and colon cancer purified nuclear fractions showed reactivity at 200 kDa in 3/30 breast and 3/20 colon cancer samples as well as purified nuclear fractions obtained from breast cancer cell lines. Conclusions: This study shows that the MUC1 extracellular domain might be translocated to the cell nucleus in breast, head and neck, and colon cancer as well as BBD., Facultad de Ciencias Médicas

Objectives: The purpose of this study was to compare risk and prognostic factors of invasive breast cancer in two Argentine populations. Patients and Methods: a total of 625 women with invasive breast cancer at different stages were studied: 270 patients from the city of La Plata, and 355 patients from the city of Neuquén. Demographic features and reproductive history were considered as risk factors, while prognostic factors included histopathological features. Statistical analysis was performed. Results: The age at diagnosis was significantly lower in Neuquén than in La Plata; stage III was observed in La Plata at a mean age of 49 years versus 54 years in Neuquén; cutaneous and/or thoracic wall invasion was found at diagnosis in Neuquén, while it was absent in all La Plata patients. Tumor size versus age showed a negative statistical significant relationship; the percentage of HER2/neu-positives in Neuquén was significantly higher than in La Plata, while estrogen/progesterone receptor status showed the contrary. Histological and nuclear grades in Neuquén compared to La Plata were significantly higher, while vascular invasion showed the converse. Considering the number of children, significant differences between groups were found, and also, patients who had breastfed presented a lower number of metastatic lymph nodes than those who had not. Conclusions: La Plata and Neuquén constitute two different populations. The factors that contribute to dividing the groups could be related to the malignant histological characteristics of the tumors, but also the length of breastfeeding and number of children could play a role., Centro de Investigaciones Inmunológicas Básicas y Aplicadas

A descriptive study was developed in an entire Argentine rural community considering breast cancer risk factors, preventive strategies and breast cancer incidence.the study comprised of 83 women. A questionnaire of 34 items was employed; a mammogram and a breast ultrasound were performed. ANOVA and Pearson correlation were employed.Mean age was 54.5 years; 69% of women were postmenopausal; 96% had children; breastfeeding was X=10 months/child; Body Mass Index (BMI) was X=27.8 kg/m(2); 13% had first-degree relatives with breast cancer; 90% of women considered mammographic screening a necessary study. One woman had presented breast cancer. Argentine screening guidelines were not followed and an inverse relationship between education level and age of first mammogram was found (p0.05). Mammographic and ultrasound studies did not reveal potential abnormalities.Peculiar social and cultural characteristics may be relevant to evaluate breast cancer risk factors in Argentina.

Indoleamine-2,3-dioxygenase (IDO) has been established as a normal mechanism of peripheral tolerance and immunosuppression. Besides, malignant tumors release microvesicles (MV) related with tumor dissemination. The aims of this study were to determine the expression of IDO in breast cancer and circulating microvesicles from breast cancer patients and to perform an in silico analysis to find genes co-expressed to IDO. One hundred and twenty-two tissue and serum breast samples (91 malignant, 21 benign, and 10 normal), and MCF7, MDA-MB-231, and T47D breast cancer cell lines were included. Standard immunohistochemistry (IHC), immunocytochemistry (ICC), Western blot (WB), and RT-PCR were employed. Microvesicle isolation from plasma samples was obtained by serial centrifugation and ultracentrifugation. By IHC, 60 % breast cancer, 43 % benign, and 20 % normal samples were positive. Significant differences were found among normal, benign, and malignant samples. Breast cancer stages I, II, and III expressed IDO in 42, 66, and 71 % of samples, respectively, while breast cancer cell lines also reacted; by WB, 9/25 microvesicles fractions showed bands at 42 kD. In silico analysis of IDO 1 gene expression in breast cancer showed its association with several genes related to immune response and apoptosis. Moreover, IDO and co-expressed genes were found predominately in basal and erbB2 subtypes. The cumulative data indicate a high expression of IDO in breast cancer which increased with higher stages. Furthermore, IDO was found in association with circulating breast cancer MV, while experimental and in silico gene expression revealed that IDO was mainly expressed in a triple-negative subgroup. Fil: Isla Larrain, Marina Teresita. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina Fil: Rabassa, Martín Enrique. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina Fil: Lacunza, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina Fil: Barbera, A. Breast Clinic. La Plata; Argentina Fil: Cretón, A.. Breast Clinic. La Plata; Argentina Fil: Segal Eiras, Amada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina Fil: Croce, María Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina

An immunological analysis to study MUC1 mucin core protein and carbohydrate associated antigens as tissue tumor markers in head and neck carcinoma was performed. Twenty nine patients with the following tumor localizations were included: tongue (n=10), larynx (n=8), oral cavity (n=4), maxillary sinus (n=3), tonsillar ring (n=3) and pharynx (n=1); seven samples of epithelium obtained from normal organs at the same localizations were studied as controls. Immunohistochemical analysis was performed following standard procedures and reaction was graded according to staining intensity and distribution. From each tissue section, membrane, cytoplasmic and nuclear moieties were obtained by differential centrifugation with subsequent fractionation by density gradient centrifugation (6M guanidium chloride-CsCl); subcellular moieties and CsCl derived fractions were analyzed by immunoblotting. Monoclonal antibodies (MAbs) reacting with the core protein of MUCI (C595) and associated carbohydrate antigens were: Tn, 83D4 MAb; Lewis y antigen (Le y), C14 MAb; Lewis x antigen (Le x), KM380 MAb and sialyl Lewis x (sLe x), KM93 MAb. Statistical analysis was undertaken by Spearman rank correlation. In tumor samples, the immunohis-tochemical identification of MUCl core protein and associated antigens was extended; differences were found in the pattern and intensity of expression; results were corroborated by immunoblotting although in a few samples there was not coincidence between both methods. Localization, tumor mass or node involvement did not show significant differences for any of the antigens studied. Conclusions: 1) head and neck carcinoma expressed MUCI and associated carbohydrate antigens in high levels; 2) no relationship between antigenic expression and tumor status was found.

Serum from patients with different malignancies contain an abnormal concentration of a a1-acidic-glycoprotein (AAG) and also, increased levels of AAG are associated with the presence of tumor mass. In the present report, serum levels of AAG were measured by radial immunodiffusion in squamous cell carcinoma of the head and neck (SCCHN) patients taking into account disease status parameters such as tumor localization, stage and extension of disease. Immunohistochemical methods, SDS-PAGE and Western-blotting were employed to study the expression of AAG and a carbohydrate related antigen (sialyl Lewis x) in tumor tissues and derived fractions. AAG showed abnormal levels in 7/15 oral cavity tumor patients sera, 2/5 oropharynx and 5/10 larynx tumors; increased AAG serum levels belonged to patients with disseminated disease. On the other hand, the presence of AAG and sialyl Lewis x were demonstrated in carcinoma cells and in derived fractions from tumor tissues belonging to patients with elevated AAG serum levels. In the present study, we have found elevated levels of AAG in serum samples from SCCHN patients; these neoplastic cells are capable to express AAG.

There is convincing epidemiological evidence that multiparity provides protection against the development of breast cancer. In the present study we evaluated the levels of MUC1 and MUC1 circulating immune complexes (MUC1-CIC) in 135 serum samples obtained from healthy women. The study population included 13 women who had never been pregnant, 31 primiparous pregnant women, 36 multiparous pregnant women who had lactated, 5 multiparous pregnant women who had never lactated, 24 multiparous non-pregnant women who were lactating at the time of the study, 24 multiparous non-pregnant women who had lactated, and 2 multiparous non-pregnant women who had never lactated. The purpose of this work was to detect MUC1 variations during pregnancy and lactation as well as to study the possible induction of a humoral immune response against MUC1 in these conditions. We employed ELISA techniques to measure MUC1 (CASA test) and MUC1-CIC (IgM and IgG) using two anti-MUC1 monoclonal antibodies (MAbs): C595 and SM3. Statistical analysis was performed using the ANOVA test. The pooled results pertaining to pregnant versus non-pregnant women were compared and significant differences were observed in MUC1 and MUC1-CIC-IgM levels detected with both MAbs; the MUC1-CIC-IgG levels detected with C595 were increased in the pregnant group while the MUC1-CIC-IgG levels detected with SM3 did not show any significant differences. When the results were compared between lactating and non-lactating women, no significant differences were found. In conclusion, MUC1 and MUC1-CIC-IgM, detected with both MAbs, and MUC1-CIC-IgG levels detected with the MAb C595 are apparently induced by pregnancy.

The most common clinical form of lung cancer is a disseminated disease with distant metastases; several years of cancer progression precede presentation, and this ultimately limits the efficacy of curative therapy. In this immunohistochemical study, we examined a mucinous adenocarcinoma cell line, maintained by xenogeneic transplantation, and a spontaneous metastatic variant which produces distant tumors (in liver, spleen and kidney). The aim was to investigate possible parameters which characterize the metastatic process. Histopathological comparison between the two subcutaneous transplanted tumor lines showed that both lines presented a similar cellular morphology, a different pattern of cellular growth and an increased vascularization in the metastatic line with respect to its parent. All the tumor sections expressed differential immune reactivity with monoclonal antibodies against Lewis y (MAb C14), sialyl-Lewis x (MAb SNH3) and Lewis x (MAb FH2) determinants. Neither expressed MUC 1 mucins detectable with monoclonal antibodies reactive with the mucin protein core (MAbs C595 and SM3) nor was carcinoembryonic antigen (MAb C365) expressed. Neoplastic cells were reactive with an anti-pan cytokeratin monoclonal antibody confirming their epithelial histogenesis. Our findings have been evaluated with respect to defining metastatic phenotypes in lung cancer by examination of distinct histopathological and immunological parameters.

Circulating immune complex (CIC) levels and their antibody and antigenic composition were evaluated in patients with leprosy as well as in any individuals living with them; they were precipitated with 3.5% polyethylene glycol (PEG) and, after affinity chromatography isolation and purification, analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot with monoclonal antibodies (Mabs). The presence of CICs was demonstrated throughout the clinical and immunopathological leprosy spectrum at levels related to bacterial load, and in leprosy patients they showed a positive correlation with specific anti-PGL and anti-65 kDa antibodies. The isolation and analysis, however, failed to identify any Mycobacterium leprae antigenic components; although two specific antibodies anti-PGL-1 and anti-65 kDa were identified as possible CIC constituents and may be potentially useful in the follow-up of leprosy patients, especially to check bacterial load evolution, PGL-1 being an authentic antigen of this mycobacterium. Also, the involvement of 65 kDa in CICs, being homologous with the human heat shock protein (HSP) 60 kDa family, suggests an autoimmune mechanism in leprosy pathogenesis. Furthermore, those results support the inclusion of CIC antibody reactivity studies to enhance the sensitivity of serology.

MUC1 es una glicoproteína heterodimérica formada por dos subunidades, la MUC1-N (extracelular) y la MUC1-C (transmembrana y cola citoplasmática). En las células neoplásicas malignas MUC1 se encuentra sobre-expresada y la glicosilación de MUC1-N está alterada. Se ha comprobado que MUC1-C interactúa con diversas moléculas en el citoplasma y se la hallado también en el núcleo; por lo contrario, se ha considerado que MUC1-N no se ubica en el núcleo celular. Objetivo: Estudiar la expresión de MUC1-N en el núcleo celular de tumores de mama, colon y cabeza y cuello., Facultad de Ciencias Médicas