EVALUATION OF THE EXPRESSION OF THE LOW WEIGHT HEAT SHOCK PROTEIN αB-CRYSTALLIN IN PULMONARY NEUROENDOCRINE TUMOURS

alpha B-crystallin is a major heat-inducible small heat shock protein, which is supposed to be implicated in tumour cell proliferation, differentiation, invasion, metastasis and apoptosis. Still the expression pattern of the phosphorylated on serin 59 form of alpha B-crystallin in lung cancer is not yet investigated. The aim of the present work is to study this pattern in different histological subtypes of pulmonary neuroendocrine tumours (pNETs). Surgically resected specimens from 143 patients with pNETs were studied. The histological subtype, pathological Tumour-Node-Metastasis stage and the immunohistochemical expression of phosphorylated alpha B-crystallin were evaluated. We demonstrated that the nucleus was the major localization site of the protein although there were some rare cases showing also diffuse cytoplasmic expression. High grade pNETs (small cell lung carcinoma and large cell neuroendocrine carcinoma) showed nuclear expression in all cases but most frequently it was in less than 50% of the tumour cells; cytoplasmic expression was shown in single cases. Just the opposite was observed in low and intermediate grade pNETs (typical carcinoids and atypical carcinoids) nuclear expression was not seen in all of the cases, but when it was present it was in almost all tumour cells; the cases expressing phosphorylated alpha B-crystallin also in the cytoplasm were mainly typical carcinoids. We demonstrated that cytoplasmic expression was associated with earlier stage and absence of metastases, which may determine it as a potential marker for a favourable prognosis in patients. We conclude that phosphorylated alpha B-crystallin probably plays a major role in pNETs biology, it may be associated with tumour grade, it may have a prognostic value, and it may be used as future target for therapy.