Diagnostic value of metabolic phenotypes in malignant pleural effusions

Abstract

BACKGROUND: The sensitivity of conventional cytology for the detection of malignant cells in pleural effusion is insufficient. GLUT1 and CAIX are the hallmarks of metabolic change in cancer cells. The aim of this study was to evaluate the usefulness of GLUT1 and CAIX expression to the detection of cancer cells in pleural effusions. METHODS: A total of 150 pleural effusions were subjected to immunocytochemical staining for GLUT1 and CAIX expression. According to their cytological diagnosis and etiology, these included 58 benign effusions, 38 probable malignant effusions, 7 atypical effusions, and 47 malignant effusions,. RESULTS: None of the benign effusions showed GLUT1 or CAIX expression, but probable malignant effusions and malignant effusions significantly expressed GLUT1 and CAIX with a positive result in 74.5% and 63.8% of the malignant effusions, respectively, with 100% specificity. When the combination of both markers was evaluated, GLUT1 and CAIX displayed a higher diagnostic performance, ie, a sensitivity of 76.6%, specificity of 100%, and accuracy of 89.5%. A statistically significant positive correlation between GLUT1 and CAIX expression was observed. In addition, 18% of cases with cells resembling mesothelial cell hyperplasia in probable malignant effusions and 71.4% of cases with atypical cells of uncertain significance in atypical effusions were highlighted on GLUT1 or/and CAIX immunocytochemical stains. CONCLUSIONS: Immunocytochemical staining for GLUT1 and CAIX may be a complementary tool for the detection of malignant pleural effusions and is helpful in distinguishing cancer cells from reactive mesothelial cells. A combination of GLUT1 and CAIX immunocytochemical staining can give a higher diagnostic performance. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.

Targeting carbonic anhydrase IX depletes breast cancer stem cells within the hypoxic niche

“…46 Importantly, CAIX activity is required for primary metastatic breast cancer cell growth under hypoxic conditions that favor the expansion of CSCs and previously noted to be highly appropriate for assessing the sensitivity of CSCs to therapeutic agents. 21 These findings further confirm the relevance of CAIX-specific pharmacologic inhibitors as future treatment for metastatic breast cancer.…”

“…In each sample, metastatic tumor cells displayed highly specific staining for CAIX, which was notably absent from other cell populations, similar to previous reports. 46 Subsequently, we cultured three PE samples to assess the functional requirement for CAIX activity. Viable PE samples from three different patients were collected and cultured under hypoxic TS-forming conditions confirmed as highly appropriate for assessing the sensitivity of CSCs to therapeutic agents.…”

Carbonic Anhydrase IX (CAIX) Does Not Differentiate Between Benign and Malignant Mesothelium

“…10 In this regard, CAIX is commonly used as an ancillary immunostain to aid in the diagnosis of metastatic renal cell carcinoma. 4 Recent studies 6,11 showed that higher CAIX levels by immunocytochemical studies and/or by enzyme-linked immunosorbent assays are seen in malignant effusions in contrast to benign effusions. These studies suggest that benign-appearing, CAIX-immunoreactive, "mesotheliallike" cells seen on a Papanicolaou stain are likely to represent atypical/malignant cells.…”

“…4,5 A recent article noted that immunostaining for CAIX on pleural effusion samples can serve as a complementary tool in distinguishing carcinoma from reactive mesothelial cells. 6 In addition, two studies noted CAIX expression in malignant pleural mesotheliomas and in metastatic renal cell carcinoma to the lung. 2,7 Furthermore, Ramsey et al 7 also observed CAIX immunostaining in one case of mesothelial hyperplasia of the pleura.…”

The diagnostic value of survivin in malignant pleural effusion: A meta-analysis

“…However, the sensitivity of these noninvasive techniques is only 40-70% [3]. The sensitivity of conventional cytology for the detection of malignant cells in pleural effusion is insufficient [4].…”