title: LKB1 protein expression in neuroendocrine tumors of the lung.
abstract: During a recent investigation of LKB1 gene abnormality in lung lesions, strong expression of LKB1 protein in normal neuroendocrine (NE) cells of the bronchial epithelium was found. Because LKB1 functions as a tumor suppressor gene, the question of whether alteration of LKB1 expression is related to the development of pulmonary NE tumors of various grades was investigated. LKB1 immunohistochemistry was examined in a total of 68 primary pulmonary NE tumors consisting of 30 specimens of small cell lung carcinoma (SCLC), 23 large cell neuroendocrine carcinomas (LCNEC), two atypical carcinoids, and 13 typical carcinoids. Loss or low expression (<20% immunoreactive cells) of LKB1 protein expression was more frequently observed in high-grade NE tumors (SCLC and LCNEC; 45/53, 84.9%) than in typical and atypical carcinoids (3/15; 20%). The difference in LKB1 immunoreactivity between the high-grade NE tumors and the carcinoid group was statistically significant (P < 0.0001). In conclusion, marked reduction of LKB1 expression in high-grade NE tumors of the lung suggests a possible role of LKB1 inactivation in its tumorigenesis. Although a few previous studies indicated rare genetic alterations of LKB1 in SCLC, further studies including analysis of other NE tumors and focusing on epigenetic abnormalities of LKB1 gene are warranted.
authors.affiliation: Department of Diagnostic Pathology, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Randa Mahmoud Sobhi
authors.initials: RM
authors.lastname: Amin
authors.forename: Kenzo
authors.initials: K
authors.lastname: Hiroshima
authors.forename: Akira
authors.initials: A
authors.lastname: Iyoda
authors.forename: Kazuei
authors.initials: K
authors.lastname: Hoshi
authors.forename: Koichi
authors.initials: K
authors.lastname: Honma
authors.forename: Motoo
authors.initials: M
authors.lastname: Kuroki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kokubo
authors.forename: Takehiko
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyagi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nakatani
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002276:Carcinoid Tumor / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D018288:Carcinoma, Small Cell / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases