Abstract
BackgroundHNSCC progression to adjacent tissue and nodes may be mediated by altered glycoproteins and glycolipids such as MUC1 mucin. This report constitutes a detailed statistical study about MUC1 expression and anti-MUC1 immune responses in relation to different clinical and pathological parameters which may be useful to develop new anti HNSCC therapeutic strategies.Patients and methodsFifty three pre treatment HNSCC patients were included: 26 (49.1%) bearing oral cavity tumors, 17 (32.1%) localized in the larynx and 10 (18.8%) in the pharynx. Three patients (5.7%) were at stage I, 5 (9.4%) stage II, 15 (28.3%) stage III and 30 (56.6%) at stage IV. MUC1 tumor expression was studied by immunohistochemistry employing two anti-MUC1 antibodies: CT33, anti cytoplasmic tail MUC1 polyclonal antibody (Ab) and C595 anti-peptidic core MUC1 monoclonal antibody. Serum levels of MUC1 and free anti-MUC1 antibodies were detected by ELISA and circulating immune complexes (CIC) by precipitation in polyethylene glycol (PEG) 3.5%; MUC1 isolation from circulating immune complexes was performed by protein A-sepharose CL-4B affinity chromatography followed by SDS-PAGE and Western blot. Statistical analysis consisted in Multivariate Principal Component Analysis (PCA); ANOVA test (Tukey's test) was employed to find differences among groups; nonparametrical correlations (Kendall's Tau) were applied when necessary. Statistical significance was set to p < 0.05 in all cases.ResultsMUC1 cytoplasmic tail was detected in 40/50 (80%) and MUC1 protein core in 9/50 (18%) samples while serum MUC1 levels were elevated in 8/53 (15%) patients. A significant statistical correlation was found between MUC1 serum levels and anti-MUC1 IgG free antibodies, while a negative correlation between MUC1 serum levels and anti-MUC1 IgM free antibodies was found. Circulating immune complexes were elevated in 16/53 (30%) samples and were also statistically associated with advanced tumor stage. MUC1 was identified as an antigenic component of IgG circulating immune complexes. Moreover, poorly differentiated tumors were inversely correlated with tumor and serum MUC1 detection and positively correlated with node involvement and tumor mass.ConclusionPossibly, tumor cells produce MUC1 mucin which is liberated to the circulation and captured by IgG antibodies forming MUC1-IgG-CIC. Another interesting conclusion is that poorly differentiated tumors are inversely correlated with tumor and serum MUC1 detection.
Highlights
head and neck squamous cell carcinoma (HNSCC) progression to adjacent tissue and nodes may be mediated by altered glycoproteins and glycolipids such as MUC1 mucin
MUC1 was identified as an antigenic component of IgG circulating immune complexes
There were no statistically significant differences in MUC1 cytoplasmic tail expression related to tumor stage, localization or differentiation, a clear tendency of negative CT33 reaction was found in advanced stage tumors while nuclear staining was associated with poorly differentiated tumor areas
Summary
HNSCC progression to adjacent tissue and nodes may be mediated by altered glycoproteins and glycolipids such as MUC1 mucin. HNSCC localization consists about 40% in the oral cavity, 15% in the pharynx, 25% in the larynx and the rest sites such as salivary glands and thyroid [1,2]. Data obtained from argentinian records show some differences compared with data found in other countries since the most frequent localization has been larynx (1665/3127, 53%) followed by oral cavity (1035/3127, 33%) and pharynx showing 427/3127, 14%. HNSCC mainly progress to adjacent tissue and nodes while distant metastasis is a late event. The ability of tumor cells to invade is an acquired and progressive phenomenon mediated, in many cases, by the alteration of membrane glycoproteins such as mucins.
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