Immunohistochemical Analysis of Lung Carcinomas With Pure or Partial Bronchioloalveolar Differentiation

Abstract

Context.—In 1999, the World Health Organization redefined bronchioloalveolar carcinomas (BACs) as those neoplasms with only a pure lepidic growth pattern and no invasion. Objectives.—The present study examined 45 lung cancers with a BAC component (1) to determine whether these tumors would be classified as BACs by current World Health Organization standards, (2) to quantitate the BAC component within these tumors, and (3) to see if phenotypic differences exist between the so-called invasive and noninvasive regions of these tumors. Design.—Retrospective review of hematoxylin-eosin–stained slides and classification of histologic grade, tumor subtype, and percentage of pure BAC pattern, with further characterization by immunohistochemical staining for thyroid transcription factor 1, cytokeratin 7, cytokeratin 20, and Ki-67 antibodies. Results.—Only 7 (15.6%) of the 45 tumors examined could be classified as BAC by current strict World Health Organization criteria. Those tumors, classified as nonmucinous and mixed, showed similar immunohistochemical staining for cytokeratin 7, cytokeratin 20, and thyroid transcription factor 1; mucinous tumors showed disparate staining. Significant differences in immunohistochemical staining and tumor cell proliferation were seen for the regions of tumors designated as lepidic, infiltrative, and leading edge and for the regions of tumors with different histologic grades (ie, well, moderately, and poorly differentiated). Conclusions.—Nonmucinous and mixed BACs are phenotypically similar and show identical immunohistochemical staining patterns; mucinous tumors, on the other hand, show disparate immunohistochemical staining. Pulmonary neoplasms designated as adenocarcinomas with a BAC component represent a heterogenous group with a range of cell types, differentiation, growth, and immunophenotypes. Within an individual neoplasm, there are regional differences in these parameters as well.

The role of ZEB1 in the inflammation‐induced promotion of EMT in HNSCC

“…Several E‐cadherin transcriptional repressors have been characterized (ZEB1, Snail, E12/E47, Slug, Twist, and SIP‐1) and shown to interact with proximal E‐boxes of the E‐cadherin promoter 13 . Among these repressors, ZEB1 and Snail expression were significantly correlated with reduced expression of E‐cadherin and EMT transition in tumor cells.…”

“…Four‐μm‐thick tissue sections were cut, deparaffinized in xylene, rehydrated in alcohols, and washed twice with water. Samples were then incubated in 0.01 M citrate (pH 6.0) and 0.01 M EDTA (pH 8.0) for 25 minutes in a steamer to unmask antigens for E‐cadherin and COX‐2, and ZEB1, respectively, as previously described 13 , 14 . Following cooling to room temperature and rinsing with distilled water, samples were treated for 15 minutes with three percent H 2 O 2 diluted in methanol to block endogenous peroxidase.…”

“…Samples were then incubated in 0.01 M citrate (pH 6.0) and 0.01 M EDTA (pH 8.0) for 25 minutes in a steamer to unmask antigens for E-cadherin and COX-2, and ZEB1, respectively, as previously described. 13,14 Following cooling to room temperature and rinsing with distilled water, samples were treated for 15 minutes with three percent H 2 O 2 diluted in methanol to block endogenous peroxidase. Subsequently, the slides were washed in distilled water, then in phosphate-buffered saline with Tween-20 (0.1%) (PBST) for five minutes.…”

The Bronchioloalveolar Carcinoma and Peripheral Adenocarcinoma Spectrum of Diseases

“…1,46 Furthermore, most tumors reported to be BAC by the increasingly used fine needle aspiration biopsy or transbronchial biopsy 28,47 were probably ADC-WBF because suf-ficient tumor was not provided to definitively exclude invasion. 48,49 This can be a significant problem because up to 80% of ADCs arising in peripheral airways are currently "adenocarcinoma with mixed subtypes" and usually contain some BAC.…”