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SUMMARY OBJECTIVE: Breast cancer is the most common malignancy in women. In the treatment of these patients, pathological complete response is defined as the absence of invasive cancer in breast or lymph node tissue after the completion of neoadjuvant chemotherapy. In this study, we aimed to investigate the relationship of enhancer of zeste homolog 2 and mucin 1 expressions with pathological complete response in patients with breast cancer receiving neoadjuvant chemotherapy. METHODS: A total of 151 patients were included in the study. Enhancer of zeste homolog 2 and mucin 1 expressions were evaluated in the biopsy materials pre-neoadjuvant chemotherapy and post-neoadjuvant chemotherapy surgical material, and their relationship with pathological complete response was investigated. RESULTS: The pathological complete response rates were significantly higher among the hormone receptor-negative patients, those with a high Ki-67 score, and patients with HER2-positive. Higher pathological complete response rates were obtained from patients with enhancer of zeste homolog 2 expression positivity pre-neoadjuvant chemotherapy. In addition, after neoadjuvant chemotherapy, enhancer of zeste homolog 2 expression was found to be completely negative in materials with pathological complete response; that is, in breast tissues considered to be tumor-free. While there was no significant relationship between mucin 1 expression and pathological complete response pre-neoadjuvant chemotherapy, mucin 1 expression was determined to significantly differ between the tissues with and without pathological complete response among the surgical materials examined. CONCLUSION: In our study investigating the relationship between enhancer of zeste homolog 2 and mucin 1 expression and pathological complete response in patients who received neoadjuvant chemotherapy, we found that enhancer of zeste homolog 2 expression could be used as a predictive marker for pathological complete response. However, mucin 1 expression was not associated with pathological complete response.
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Objective:To investigate the expressions of MUC1, MUC4, MUC5AC and MUC16 in patients with first diagnosis of dry eye and their correlation with dry eye symptoms and signs.Methods:A cross-sectional study was conducted.Sixty-nine dry eye patients (69 eyes) as dry eye group and 40 normal volunteers (40 eyes) as normal control group were recruited in Xiamen Eye Center of Xiamen University, Beijing Tongren Hospital, West China Hospital of Sichuan University and Shanghai Puotuo District Center Hospital from December 2016 to May 2018.Symptoms were evaluated by Chinese dry eye questionnaire, Ocular Surface Disease Index (OSDI) and Dry Eye-Related Quality-of-Life Score Questionnaire (DEQS). Signs were assessed by tear film breakup time (TBUT), keratoconjunctival fluorescein sodium staining, and Schirmer I test.Conjunctival cells were collected by conjunctival impression cytology.The expression levels of MUC1, MUC4, MUC5AC and MUC16 mRNA in the two groups were determined by real-time fluorescence quantitative PCR.The correlation between the mRNA levels of conjunctival mucins and dry eye symptoms and signs were analyzed by Spearman correlation analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committees of Xiamen Eye Center of Xiamen University (No.2017003), Beijing Tongren Hospital, Capital Medical University (No.TREC2016-29), West China Hospital of Sichuan University (No.2016310) and Shanghai Puotuo District Center Hospital (No.PTEC-A-2016-18-1). Written informed consent was obtained from each subject before any medical examination.Results:The expression levels of MUC1 and MUC16 mRNA in dry eye patients were 3.277(0.568, 5.790) and 1.815(1.048, 3.694), which were higher than 1.055(0.550, 2.010) and 1.024(0.541, 1.965) in normal control group (Z=819.00, P=0.008; Z=861.00, P=0.002). According to OSDI scores, MUC1 was mainly increased to 3.277(1.161, 6.226) in mild to moderate (12-32 points) dry eye patients (Z=9.04, P=0.029), and MUC16 was mainly increased to 1.968(1.074, 3.726) in severe (>32 points) dry eye patients (Z=12.24, P=0.007). MUC1 expression was positively correlated with TBUT, and was negatively correlated with corneal staining scoring and keratoconjunctival staining scoring ( r s=0.270, P=0.025; r s=-0.331, P=0.006; r s=-0.325, P=0.007). MUC16 expression was positively correlated with TBUT, and was negatively correlated with blurred vision scoring, symptom exacerbation scoring during reading, impact scoring of driving at night, impact scoring of computer and impact scoring of TV use ( r s=0.249, P=0.039; r s=-0.359, P=0.047; r s=-0.370, P=0.034; r s=-0.558, P=0.016; r s=-0.498, P=0.006; rs=-0.515, P=0.002). Conclusions:The gene expressions of MUC1 and MUC16 are higher in conjunctiva of dry eye patients.MUC1 mRNA expression is related to patients' signs.MUC16 mRNA expression is related to the quality of life of patients.
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El adenocarcinoma NOS (no especificado de otra manera) es un tumor salival sin patrón especial poco mencionado en la literatura; su diagnóstico es un desafío porque estructuralmente no se identifica con otros carcinomas salivales más definidos. Por otro lado, Ki67 es un marcador de proliferación celular que brinda información pronóstica de las neoplasias. En cuanto a la mucina humana transmembrana MUC-1 se sobre-expresa en las neoplasias malignas perdiendo su localización exclusivamente apical. Presentamos dos casos de adenocarcinoma NOS diagnosticados con H/E y correlacionamos la expresión de Ki67 y la localización y sobreexpresión de MUC-1 con su grado histológico y pronóstico. Cortes histológicos de dos adenocarcinomas NOS de parótida en mujeres de 62 y 63 años respectivamente se colorearon con H/E e inmunomarcaron para Ki67 y MUC-1. En ambos tumores predominaban estructuras ductales, algunas quísticas, cordones celulares ramificados e islotes sólidos. Las formaciones glandulares presentaban células claras y algunas de aspecto oncocítico. Había importante atipia celular, comedonecrosis, invasión perineural, áreas hemorrágicas y compromiso de los márgenes quirúrgicos. La marcación nuclear con Ki67 fue importante; MUC-1 presentó una fuerte coloración en membranas y citoplasmas. Las dos lesiones se diagnosticaron como de alto grado de malignidad. Nuestros resultados demuestran que existe una importante proliferación marcada con Ki67 y una sobre-expresión de MUC-1 asociadas a atipia celular, infiltración perineural, necrosis y compromiso de márgenes quirúrgicos, factores asociados a un peor pronóstico. El reconocimiento de este tumor es trascendente para médicos y odontólogos ya que por la ausencia de rasgos distintivos que sí presentan otros carcinomas más específicos es fundamental el diagnóstico de exclusión.
Adenocarcinoma NOS (not otherwise specified) is a no special pattern salivary tumor briefly mentioned in the literature; its diagnosis is a challenge because structurally it is not identified with other more definite salivary carcinomas. On the other hand, Ki67 is a marker of cellular proliferation that provides prognostic information of neoplasms. As for human transmembrane mucin, MUC-1 is overexpressed in malignant neoplasms, losing their exclusively apical location. We present two cases of adenocarcinoma NOS diagnosed with H/E and correlate the expression of Ki67 and the location and over-expression of MUC-1 with its histological grade and prognosis. Histological sections of two NOS adenocarcinomas of parotid in women of 62 and 63 ages respectively were stained with H/E and immunolabelled for Ki67 and MUC-1. Both are predominated by ductal structures, some cystic, branched cell cords and solid islets. The glandular formations presented clear cells and some of oncocytic appearance. There was important cellular atypia, comedonecrosis, perineural growth, haemorrhagic areas and compromise of surgical margins. Nuclear marking with Ki67 was important; MUC-1 presented a strong staining in membranes and cytoplasms. They were diagnosed as high-grade malignancy. Our results show that there is an important proliferation marked with Ki67 and overexpression of MUC-1 associated with cellular atypia, perineural growth, necrosis and compromise of surgical margins, factorsassociated with a poor prognosis. The recognition of this tumor is transcendent for physicians and dentists since, due to the absence of distinctive features that other more specific carcinomas present, the diagnosis of exclusion is essential.
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Humans , Female , Middle Aged , Parotid Neoplasms/diagnosis , Parotid Neoplasms/metabolism , Parotid Neoplasms/pathology , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Prognosis , Salivary Gland Neoplasms , Immunohistochemistry , Adenocarcinoma/diagnosis , Biomarkers, Tumor , Mucin-1/metabolism , Ki-67 Antigen/metabolism , Cell ProliferationABSTRACT
Objective:To study the inductive effect of recombinant MUC1-MBP fusion protein combined with R848 on the immune activity of T cells in the mice,and to provide experimental basis for searching the suitable adjuvants of recombinant MUC1-MBP fusion protein.Methods:A total of 21 C57BL/6 mice were randomly divided into control group(treat with normal saline),MUC1-MBP+R848 group (treated with MUC1-MBP+R848),and MUC1-MBP+baillus calmette guerin(BCG) group(treated with MUC1-MBP+BCG)(n=7).After immunized for 4-7 d,the spleen tissue was taken and the spleen indexes of the mice in various groups were measured;the stimmulus index(SI) of the mice was detected by lymphocyte proliferation response;the levels of tumor necrosis factor-γ(TNF-γ) and interleukin-4(IL-4) were detected by ELISA method;the proprotions of T lymphocyte subsets in spleen cells were analyzed by flow cytometry.Results:Compared with control group,the spleen indexes,SI,and TNF-γ levels of the mice in MUC1-MBP+ R848 and MUC1-MBP+BCG groups were significantly increased (P0.05).Compared with control group,the proprotions of CD3+T,CD4+T,and CD8+ T cells of the mice in MUC1-MBP+ R848 group and MUC1-MBP+BCG group were significantly increased(P<0.05 or P<0.01).Conclusion:Both MUC1-MBP fusion protein combined with R848 and BCG can induce the Th1 type of immune activity in the mice,and R848 is the potential candidate adjuvant for MUC1-MBP.
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Mucins(MUC)are secreted by the epithelial cells of polymer ,the height of glycosylation gly-coprotein,widely existing in the respiratory system ,digestive system,urogenital system in the mucosa epithelium and mucus secretion .The resent studies show that sticks are closely associated with tumor protein family .Among them,the sticky protein 1(CA153)and 16 mucins(CA125)has been confirmed that the abnormal expression in the bile duct carcinoma.However,there is unclear relationship between the development ,invasion,metastasis and prognosis of gallbladder .Based on the retrospective literature at home and abroad in recent years , the research progress on the sticky protein 1 and mucins 16 in the gallbladder is summarized in the present review .
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ABSTRACT DNA vaccines have been shown to be an effective approach to induce antigen-specific cellular and humoral immunity. However, the inability of DNA vaccines to elicit strong immune responses in clinical trials limits the application of DNA vaccines. Here, we developed a new DNA vaccine based on MUC1, which has been suggested as a potential target for lung cancer therapy, and we enhanced the potency of the DNA vaccine by including granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjuvant. A series of DNA plasmids encoding MUC1, human GM-CSF and their conjugates were constructed and injected into female mice intramuscularly (i.m.). This action was followed by an electric pulse. The humoral and cellular immune responses after immunization were examined by ELISA and ELISPOT, respectively. To evaluate the therapeutic efficacy of the plasmids, a mouse model with a MUC1-expressing tumor was designed. Mice vaccinated with the MUC1-GM-CSF plasmid generated the strongest MUC1-specific humoral and cellular immune responses. Furthermore, these vaccinations inhibited the growth of MUC1-expressing tumors and prolonged mouse survival. These observations emphasize the potential of GM-CSF as an adjuvant for DNA vaccines and of vaccines based on MUC1 and GM-CSF as a promising treatment for lung cancer.
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Pleomorphic adenoma (PA) is the most common salivary gland tumor and its microscopic features and histogenesis are a matter of debate. Human milk fat globule protein membrane (HMFG) monoclonal antibodies (MoAbs) comprise a set of antibodies against the mucin 1 (MUC-1) protein detected in several salivary gland tumors. Objective The aim of this study was to assess the immunoexpression of the PA neoplastic cells to MUC-1 protein using HMFG-1 and HMFG-2 MoAbs, contrasting these results with those from normal salivary gland tissue. Material and Methods Immunohistochemical detection of MUC-1 protein using HMFG-1 and HMFG-2 MoAbs was made in 5 mm thick, paraffin embedded slides, and the avidin-biotin method was used. Results Positivity to HMFG-1 and HMFG-2 MoAbs was found in ductal, squamous metaplastic and neoplastic myoepithelial cells, keratin pearls and intraductal mucous material. Two kinds of myoepithelial cells were identified: classic myoepithelial cells around ducts were negative to both MoAbs, and modified myoepithelial cells were positive to both MoAbs. This last cellular group of the analyzed tumors showed similar MUC-1 immunoexpression to ductal epithelial cells using both HMFG antibodies. Intraductal mucous secretion was also HMFG-1 and HMFG-2 positive. Conclusions Our results showed there are two kinds of myoepithelial cells in PA. The first cellular group is represented by the different kinds of neoplastic myoepithelial cells and is HMFG-positive. The second one is HMFG-negative and represented by the neoplastic myoepithelial cells located around the ducts. .
Subject(s)
Humans , Adenoma, Pleomorphic/chemistry , Antibodies, Monoclonal , Glycolipids , Glycoproteins , Membrane Proteins , Mucin-1/analysis , Salivary Gland Neoplasms/chemistry , Adenoma, Pleomorphic/pathology , Biomarkers, Tumor/analysis , Case-Control Studies , Immunohistochemistry , Paraffin Embedding , Reference Values , Salivary Gland Neoplasms/pathology , Salivary Glands/chemistry , Salivary Glands , Staining and Labeling/methodsABSTRACT
Objective To evaluate the effectiveness of ultrafiltration technology in endotoxin removal from purified recombinant MUC1-MBP fusion protein (MUC1-MBP)and to demonstrate the effect of ultrafiltration on endotoxin removal.Methods CM Sepharose FF weak cation exchange (CM)(CM group), CM combined with Phenyl Sepharose 6 FF exchange (C6)(CM+C6 group),CM combined with ultrafiltration (CM+ultrafiltration group), and CM combined with C6 and ultrafiltration (CM+C6+ultrafiltration group)were used to purify the MUC1-MBP from E.coli. and remove endotoxin;the expression level of endotoxin was detected by Chromogenic End-point Tachypleus Amebocyte Lysate.Results There was a single band at the expected molecular weight of 62 000 by SDS-PAGE analysis.and the purity>96% by Quantity One analysis.The endotoxin levels in CM group and CM +C6 group were quite high and there was no significant difference between two groups (P>0.05 );the endotoxin level in CM+ultrafiltration group was significantly lower than that in CM group, and there was significant difference (P0.05 ). Conclusion The effects of CM or CM combined with C6 on endotoxin removal are quite poor, especially C6;CM combined with ultrafiltration are quite effective on endotoxin removal,and ultrafiltration plays an important role in endotoxin removal.
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Objective To evaluate the MUC1 promoter's role in driving gene expression in pancreatic cancer and its therapeutic significance.Methods Two plasmids were made.The plasmid pEGFP-MUC1N1 contained MUC1 promoter fragment connected to the pEGFP-N1 vector with the EGFG reporter gene.The pShuttle-MUC1-EGFP plasmid contained MUC1 promoter fragment and EGFP reporter gene connected to pShuttle plasmid.Lipofectamine 2000 was used to transfect the two plasmids into cells of MUC1-positive human pancreatic cell line Panc-1 and MUC1-negative human cervical carcinoma Hela.Fluorescence microscopy and flow cytometry compared the specificity and activity of the MUC1 promoter and CMV promoter.Results Reporter gene EGFP-positive cells 48 hours after transfection with pEGFP-MUC1-N1 and pShuttleMUC1-EGFP plasmid were 69.6％ and 63.6％ respectively,in Panc-1 cells,and 4.2％ and 3.7％ respectively,in Hela cells.Conclusions MUC1 promoter can drive reporter gene activity in MUC1-positive tumor cells targeting functional expression.There is potentially a use of targeted therapy in pancreatic cancer at the genetic level.
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Objective To explore the expression of KL-6/MUC1 and the possible impact on alveolar development in lung tissue of newborn rats with hyperoxia-induced bronchopulmonary dysplasia (BPD).Methods Sixty-four newborn rats were randomly divided into 2 groups:hyperoxic group and control group.The rats in hyperoxic group were exposed to high oxygen volume fraction of 900 mL/L,and the rats in control group were exposed to normal oxygen volume fraction of 210 mL/L.The experimental control factors were the same in two groups.Eight rats were randomly selected from each group on day 1,3,7,and 14 after oxygen exposure.The alveolar development was evaluated by the number of radial alveolar count (RAC) and the alveolar area/pulmonary septal area ratio (A/S).The location,distribution,and expression of KL-6/MUC1 in the lung tissue were detected by the fluorescent immunoassay,Western blot,and reverse transcription polymerase chain reaction.Results Compared with the control group,the RAC in hyperoxic group decreased on day 3 and continued to decline on day 14.The A/S in hyperoxic group increased on day 7 and peaked on day 14 (P ＜0.05).KL-6/MUC1 expressed in both bronchial epithelial cells and alveolar epithelial cells of newborn rats.KL-6/MUC1 protein in hyperoxic group peaked on day 1 and decreased later,which was higher than that of the control group (P ＜ 0.05),the level of KL-6/MUC1 was positively correlated with RAC (r =0.707,P ＜ 0.05)and negatively correlated with A/S(r =-0.716,P ＜ 0.05).MUC1 mRNA in hyperoxic group was slightly higher than that in control group,but no significant inter-or intra-group difference was observed (P ＞ 0.05).Conclusions The highest expression of KL-6/MUC1 can be observed in the early phase of hyperoxic exposure,and it decreases to the lowest on the key point of pulmonary development.KL-6/MUC1 may play an important role in the alveolar development.
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PURPOSE: Mucins are members of the glycoprotein family expressed in benign and malignant epithelial cells. The aim of this study is to evaluate the relationships between the expression of mucins in breast ductal carcinoma and clinicopathologic parameters. METHODS: We constructed tumor microarrays based on 240 cases of invasive ductal carcinoma and 40 cases of ductal carcinoma in situ (DCIS) using formalin fixed, paraffin embedded tissues. We examined the expressions of MUC1, MUC2, MUC5AC, and MUC6 by immunohistochemistry. RESULTS: MUC1 demonstrated cytoplasmic, membranous, apical, and combinative expressions. Other mucins demonstrated cytoplasmic expression. In invasive ductal carcinoma, MUC1, MUC2, MUC5AC, and MUC6 were expressed in 93.6%, 6.2%, 4.8%, and 12.4% of cases, respectively; these rates were slightly, but not significantly, higher than observed in cases of DCIS. MUC1 expression was associated with estrogen receptor (ER) expression and negative MUC1 expression was associated with triple negativity. MUC6 expression was correlated with higher histologic grade, lymphatic invasion, lymph node metastasis, and HER2 positivity. No associations with any other clinicopathologic parameters were observed. CONCLUSION: Most invasive ductal carcinomas of the breast express MUC1, and this expression is associated with ER expression. MUC6 expression is correlated with some clinicopathologic parameters that are indicators of poor prognosis. To evaluate the role of MUC6 as a potential biomarker, further studies are warranted.
Subject(s)
Humans , Breast , Breast Neoplasms , Carcinoma, Ductal , Carcinoma, Intraductal, Noninfiltrating , Cytoplasm , Epithelial Cells , Estrogens , Formaldehyde , Glycoproteins , Lymph Nodes , Mucins , Neoplasm Metastasis , Paraffin , PrognosisABSTRACT
Objective To explore the molecular mechanism for the self-limitation of adenoviral infections in human airway,the different impacts of adenovirus serotype 5 ( Ad5 ) and serotype 7 ( Ad7 ) infections on mucin 1 ( MUC1 ) expression in airway epithelial cells were preliminarily investigated.Methods The Ad5 and the Ad7 infection models were established in A549 cell line.qRT-PCR was performed to determine the transcription of MUC1 mRNA,and the expression of MUC1 in A549 cells infected by Ad5 or Ad7 was by detected Western blot.Results An up-regulation of the MUC1 mRNA level were observed after Ad5 infection for 6 h(P＜0.05 ),and the protein expression level of MUC1 increased in a time-dependent manner in 48 hours of Ad5 infection,while similar response of MUC1 mRNA was absent in Ad7 infection (6 h),even after prolonged (20 h) treatment ( P ＞ 0.05 ).Conclusion This study reveals an up-regulation of MUC1 expression as one of the early immune response to Ad5 infection,which implies that MUC1 may function fully or partially as an anti-inflammatory factor in the self-limitation effect of Ad5 infection.However,type7 adenoviral infection,may introduce a mechanism otherwise,but through MUC1.
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Objective To investigate the expression of MUC-1 and CD44v6 in breast carcinoma and its diagnostic value.Methods 93 cases of breast carcinoma were examined by immunohistochemical method for MUC-1 and CD44v6.Results The positive rates of MUC-1 and CD44v6 were 71.0 ％ (66/93) and 63.4 ％ (59/93),respectively.The expression of MUC-1 in breast carcinoma was correlated with histologic differentiation (14.3 ％,69.4 ％,100.0 ％) and lymph node metastasis (22.9 ％,100.0 ％) (x2 =36.147,63.047,both P ＜ 0.0001),but had no relationship with the type of breast carcinoma,tumor clinical stages,and tumor size (all P ＞ 0.05).The expression of CD44v6 in breast carcinoma was correlated with tumor clinical stages (6.3 ％,64.6 ％,93.1％) and lymphnode metastasis (20.0 ％,89.7 ％) (x2 =9.507,45.662,both P＜0.05),but had no relationship with tumor type,tumor clinical stages and tumor size (all P ＞ 0.05).Conclusion MUC-1 and CD44v6 may play important roles in the development of breast carcinoma and the biologic behavior of breast carcinoma may be closely related with over expression of MUC-1 and CD44v6 protein.MUC-1 and CD44v6 can be used to predict the prognosis and direct the treatment of breast carcinoma.
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BACKGROUND: Recent reports have indicated that overexpression of mucin (MUC) 1 and/or MUC4 correlates with the occurrence and progression of extra-hepatobiliary malignancy. In this study, we investigated the expression of MUC1 and MUC4 and their prognostic significance in gallbladder adenocarcinoma. METHODS: We examined 54 surgical gallbladder adenocarcinoma samples by immunohistochemistry for MUC1 and MUC4 expression. Staining was evaluated as a sum score of extent and intensity, dividing the samples into low and high expression groups. RESULTS: The low expression group for both MUC1 and MUC4 was 10 samples (18.5%), and the high expression group was 44 samples (81.5%). High MUC1 expression was significantly correlated with more differentiated tumors (p=0.033), whereas high expression of MUC4 correlated with negative nodal status (p=0.012). Other pathological features were not correlated with MUC expression. Multivariate cox regression analysis showed that neither MUC1 nor MUC4 expression correlated with survival. CONCLUSIONS: Although there were some correlations found, a prognostic role for either MUC1 or MUC4 expression in gallbladder carcinoma was not identified in this study. Further investigation is required.
Subject(s)
Adenocarcinoma , Gallbladder , Immunohistochemistry , MucinsABSTRACT
Objective To determine the serum KL-6 level in patients with pancreatic carcinoma and investigate its diagnostic value. Methods The data of 53 pancreatic carcinoma (PC) patients; 68 chronic pancreatitis (CP) patients and 51 patients with high risks of pancreatic cancer (HR) with complete follow-up data were studied, and 50 healthy volunteers were used as controls. ELISA was used to measure the serum levels of KL-6, MUC4, and CA50. Radioimmunoassay methods were used to measure the serum CA19-9 levels. The sensitivity and specificity of KL-6 for the diagnosis of PC were determined, and the relationship between its levels and clinicopathologic parameters, patients' outcome were analyzed. Results The serum KL-6 levels were (753±548), (135±93), (105±55) and (99±50) U/ml in PC group, CP group, HR group and control group, and the value in PC group was significantly higher than those in other 3 groups (P 232 U/ml as the cut-off point, the sensitivity and specificity of KL-6 for the diagnosis of PC was 96% and 94%. Using >244 U/ml as the cut-off point, the sensitivity and specificity of KL-6 for the diagnosis of PC was 97% and 91%. The clinical value of KL-6 was higher than those of CA19-9, CASO and MUC4. The serum level of KL-6 was not associated with clinicopathologic parameters. The median survival of patients with serum level of KL-6 =300 U/ml was (9.3 ±1.2) months, which was significantly longer than that in patients with serum level of KL-6 >300 U/ml [ (4.6 ±0.7) months, P =0.006]. Conclusions KL-6 might be a useful serological marker of pancreatic cancer, and it may play a role in the differential diagnosis between pancreatic cancer and chronic pancreatitis.
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Objective: To investigate the expression of protein MUC1 and MUC2 in intraductal papillary mucinous neoplasms (IPMNs) and its significance. Methods: Immunohistochemical method (En Vision) was used to analyze the expression of protein MUC1 and MUC2 in 18 IPMNs and 9 pancreatic ductal adenocarcinomas. Results: Expression of protein MUC1 was detected in 4 of the 18 (22%) IPMNs (including 1 with pancreatic intraductal papillary-mucinous carcinoma) and all the 9 (100%) the pancreatic ductal adenocarcinomas, with the latter significantly higher than the former(P<0.01). Expression of protein MUC2 was detected in 17 of the 18 (94.4%) IPMNs and in 1 of the 9 (11.1%) pancreatic ductal adenocarcinomas, with the former significantly higher than the latter(P< 0.01). The expression levels of MUC2 were significantly different in IPMNs of different types (IPMA, IPMB, and IPMC, P<0.05). Conclusion: IPMNs have high expression of MUC2 and the expression is associated with the pathological types of IPMN. MUC1 expression may serve as a marker of malignant IPMNs and is worth further studying.
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BACKGROUND AND OBJECTIVES: The diagnosis of thyroid nodular diseases is critical in clinical management. Fine needle aspiration cytology and ultrasound-guided core needle biopsy are widely considered as diagnostic techniques in assessment of thyroid nodular diseases. Because of the histological similarity of follicular patterned thyroid lesions, the differential diagnosis between some thyroid lesions is often difficult to determine, even with permanent sections. For this reason, we assessed diagnostic usefulness of immunohistochemical staining for the three potential markers of malignant thyroid nodule, Galectin-3, MUC1 and EGFR (Epidermal growth factor receptor) in the tissue obtained by surgery. SUBJECTS AND METHOD: The immunohistochemical expression of galectin-3, MUC1 and EGFR was evaluated in 76 thyroid lesions obtained by surgery to assess their potential as markers in differential diagnosis of thyroid nodule. The following were studied: 20 cases of papillary carcinoma, 16 cases of follicular carcinoma, 20 cases of follicular adenoma and 20 cases of adenomatous goiter. RESULTS: The expression of Galectin-3 was stronger in malignant thyroid nodules, especially in papillary carcinoma, than in benign thyroid nodules. However, there were no significant differences in the expression rates of MUC1 and EGFR between malignant thyroid nodules and benign thyroid nodules. The expression of MUC1 and EGFR was weaker in follicular neoplasm than in other thyroid nodules. CONCLUSION: Galectin-3 was a reliable marker for papillary carcinoma. The expression of MUC1 and EGFR was increased in the papillary carcinoma and goiter, so if we could selectively identify cytoplasm MUC1, we could distinguish papillary carcinoma from the goiter.
Subject(s)
Adenoma , Biopsy, Fine-Needle , Biopsy, Large-Core Needle , Carcinoma, Papillary , Cytoplasm , Diagnosis, Differential , Epidermal Growth Factor , Galectin 3 , Goiter , ErbB Receptors , Thyroid Gland , Thyroid NoduleABSTRACT
Many breast cancer patients develop minimal residual disease that becomes resistance to treatments, and finally are faced with relapse and progression of disease. Currently, immunotherapy has become a potential therapy in treating minimal residual disease and preventing cancer occurrence. Cancer vaccines provide a unique therapeutic modality in that they initiate a dynamic process of activating the host's own immune system. A lot of tumor specific antigens as a target of immune system were identified and some have been applied for cancer vaccine. Mucin 1 (MUC1) oncoprotein, which is overexpressed in breast cancer in contrast with normal mammary tissue, is one of the first tumor antigens shown to be a target for human tumor-specific T cells and thus a valid target for immunotherapy. MUC1 is a high-molecular-weight glycoprotein rich in serine and threonine residues that are O-glycosylated. MUC1 is expressed on glandular epithelia and on epithelial tumors. But, tumor MUC1 differs from normal MUC1 by modified glycan side chains. Over-expression and aberrant glycosylation of MUC1 antigen by epithelial tumors results in endogenous antibody responses in cancer patients to MUC1 antigen. This finding has led to the identification of MUC1 derived peptide epitopes that induce T-cell responses. MUC1 based clinical trials have used peptides, protein, DNA, pulsed dendritic cells, or glycopeptide. This review will summarize the potential utility of breast cancer immunotherapy of MUC1, as well as the structure and function.
Subject(s)
Humans , Antibody Formation , Antigens, Neoplasm , Breast , Breast Neoplasms , Cancer Vaccines , Dendritic Cells , DNA , Epitopes , Glycoproteins , Glycosylation , Immune System , Immunotherapy , Mucin-1 , Mucins , Neoplasm, Residual , Peptides , Recurrence , Serine , T-Lymphocytes , ThreonineABSTRACT
Objective To investigate the expression and clinical significance of MUC1,MUC2,MUC4 and MUC5AC in pancreatic ductal adenocarcinoma(PDA).Methods To analyze the expression profiles of MUC1,MUC2,MUC4 and MUC5AC in PDA(n=26),chronic pancreatitis(CP,n=4),normal pancreas(n=16)and intraductal papillary-mucinous neoplasm(IPMN)(n=2),solid-pseudo-papillary tumor of pancreas(SPT)(n=4),serous cystic neoplasm(SCN)(n=1)using immunohistochemistry.Results Positive staining with MUC1 Was exclusively found in normal pancreas and CP tissues(100%);the expression of MUC1,MUC4 and MUCSAC in PDA was 100%,88.5%(23/26)and 76.9%(20/26)in PDA tissue;MUC2 and MUC5AC were expressed in 2 samples of IPMN;none of the four mucins were expressed in Sfrr and SCN.There was no association between the expression of MUC4,MUC5AC and the clinicopathologic parameters in PDA(P＞0.05).Conclusions Multiple mucins were expressed in PDA.Measurement of the mucin profile including all 4 mueins(MUC1,MUC2,MUC4,and MUC5AC)may be helpful in the diagnosis and differential diagnosis of PDA.
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Objective To construct multiple myeloma mucin MUC1-2VNTR gene eukaryotic expressing vector,which provided the basic material for further study of multiple myeloma DNA vaccine.Methods MUC1-2VNTR coding gene as target gene,and a KOZAK sequence was inserted before it.Hind Ⅲ and Xba Ⅰ restriction enzyme site were inserted on both ends.Then the whole sequence was synthesized and cloned into pcDNA3.1/myc-his B vector,and the recombinant vector was identified by restriction enzyme digestion and DNA sequencing.Results Synthesized MUC1-2VNTR gene was 140 bp.Restriction enzyme digestion and DNA sequencing confirmed pcDNA3.1/MUC1-2VNTR/myc-his B including the whole exact translation frame region and MUC1-2VNTR gene.Condnsion The pcDNA3.1/MUC1-2VNTR/myc-his B has been successfully constructed,which provides the basic material for further studies of MUC1 mucin function and multiple myloma DNA vaccine.