title: Down-regulation of cytoplasmic PLZF correlates with high tumor grade and tumor aggression in non-small cell lung carcinoma.
abstract: There are currently no effective prognostic biomarkers for lung cancer. Promyelocytic leukemia zinc finger (PLZF), a transcriptional repressor, has a role in cell cycle progression and tumorigenicity in various cancers. The expression and value of PLZF in lung carcinoma, particularly in the subclass of non-small cell lung carcinoma (NSCLC), has not been studied. Our aim was to study the immunohistochemical expression of PLZF in lung adenocarcinoma and squamous cell carcinoma and correlate the alteration of PLZF expression with tumor differentiation, lymph node metastasis, tumor stage, and overall survival. A total of 296 NSCLCs being mounted on tissue microarray (181 adenocarcinomas and 91 squamous cell carcinomas) were investigated. Moderate to strong expression of PLZF was found in the cytoplasm of all the nonneoplastic respiratory epithelium and most (89.9%) well-differentiated adenocarcinoma. The proportions of moderately differentiated, poorly differentiated adenocarcinoma, and paired lymph node adenocarcinoma metastases that demonstrated negative or only weak PLZF reactivity were 75.6%, 97.2%, and 89.9%, respectively. The expression of PLZF in squamous cell carcinoma was mostly weak or absent and significantly lower than that in adenocarcinoma of the same grade (P < .0005). The loss of cytoplasmic PLZF strongly correlated with high tumor grade and lymph node metastasis in both squamous carcinoma and adenocarcinoma (P < .0001). Down-regulation of PLZF also correlated with higher tumor stage and shorter overall survival (P < .05). These results support a prognostic value for loss of cytoplasmic PLZF expression in the stratification of NSCLC and a possible role of cytoplasmic shift and down-regulation of PLZF in the pathogenesis of NSCLC.
authors: Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642. Electronic address: guang-qian_xiao@urmc.rochester.edu.
authors: Guang-Qian
authors: GQ
authors: Xiao
authors: Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642.
authors: Faqian
authors: F
authors: Li
authors: Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642.
authors: Jennifer
authors: J
authors: Findeis-Hosey
authors: Department of Biostatistics, University of Rochester Medical Center, Rochester, NY 14642.
authors: Ollivier
authors: O
authors: Hyrien
authors: Department of Pathology, Lenox Hill Hospital-NS/LIJ Health System, New York, NY 10065.
authors: Pamela D
authors: PD
authors: Unger
authors: Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642.
authors: Lu
authors: L
authors: Xiao
authors: Department of Hematology and Oncology, University of Rochester Medical Center, Rochester, NY 14642.
authors: Richard
authors: R
authors: Dunne
authors: Department of Hematology and Oncology, University of Rochester Medical Center, Rochester, NY 14642.
authors: Eric S
authors: ES
authors: Kim
authors: Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642.
authors: Qi
authors: Q
authors: Yang
authors: Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642.
authors: Loralee
authors: L
authors: McMahon
authors: Department of Pathology, Mount Sinai Medical Center, New York, NY 10029.
authors: David E
authors: DE
authors: Burstein
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness / Q000473:pathology*; D011379:Prognosis; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D015996:Survival Rate
chemical_list: D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C092037:ZBTB16 protein, human
keywords: Aggression; Cytoplasmic; Differentiation; Non–small cell lung carcinoma; PLZF