Liang-Che Chang

Immunohistochemical and molecular genetic profiling of acquired cystic disease-associated renal cell carcinoma.

Aims:u2002 Acquired cystic disease‐associated renal cell carcinoma (ACD‐associated RCC) is a unique neoplasm that specifically develops in the background of acquired cystic disease of the kidney. The aim was to analyse nine ACD‐associated RCCs from three patients to determine their immunohistochemical and molecular characteristics using immunohistochemistry, comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH).

Diagnostic significance of narrow‐band imaging for detecting high‐grade dysplasia, carcinoma in situ, and carcinoma in oral leukoplakia

To investigate the diagnostic accuracy of the established patterns of intraepithelial microvasculature of narrow‐band imaging (NBI) in diagnosing upper aerodigestive tract neoplasm of the squamous epithelium for detecting high‐grade dysplasia, carcinoma in situ, and carcinoma in oral leukoplakia.

Use of endoscopy with narrow-band imaging system in evaluating oral leukoplakia.

The purpose of this study was to analyze the relationship between clinical features of oral leukoplakia using endoscopy with broadband white light, narrow‐band imaging (NBI) illumination, and histopathology, and to discuss the clinical relevance of the NBI system.

Light sources used in evaluating oral leukoplakia: broadband white light versus narrowband imaging

This study aimed to investigate the clinical efficacy of using broadband white light (BWL) to observe morphologic appearance, narrow-band imaging (NBI) to observe intraepithelial microvasculature, and both BWL and NBI for the detection of high-grade dysplasia and carcinoma in oral leukoplakia. Among 317 patients (274 males and 43 females; aged 52.4±10.7 years), the odds ratio (95% confidence interval) for detecting high-grade dysplasia and carcinomatous lesions based on morphologic appearances of BWL, and microvasculature patterns of NBI, were 39.12 (9.33-64.10), and 97.16 (38.19-247.21), respectively, which were significantly better than BWL (p<1×10(-15)). The sensitivity, specificity, positive and negative predictive values, and accuracy of use of traditional BWL classification, NBI classification, and combined BWL and NBI classification for detecting high-grade dysplasia and carcinomatous lesions were 96.30, 60.08, 33.12, 98.75, 66.25, 39.92, and 3.70%; 87.04, 93.54, 73.44, 97.23, and 92.43%; and 100.00, 60.08, 33.96, 100.00, and 66.88%, respectively. In conclusion, the diagnostic accuracy by NBI classification of oral leukoplakia based on the intraepithelial microvasculature patterns is significantly better than BWL indicating that NBI is a promising non-invasive tool in detecting high-grade dysplasia and carcinomatous lesions in oral leukoplakia.

Clinical Appraisal of Endoscopy with Narrow-Band Imaging System in the Evaluation and Management of Homogeneous Oral Leukoplakia

Purpose: To evaluate the clinical usefulness of endoscopy with a narrow-band imaging (NBI) system for the evaluation and management of homogeneous oral leukoplakia. Methods: The chart records, morphology of vascular architecture of NBI, and histopathology of patients with homogeneous leukoplakia were retrospectively reviewed and analyzed. Results: A total of 160 patients, with an average age of 50.96 ± 10.25 years, were enrolled. In 35 cases of thin leukoplakia, only intraepithelium papillary capillary loop (IPCL) type I was shown by NBI, and only squamous hyperplasia was revealed pathologically. In 125 cases of thick leukoplakia, IPCL type I was found in 94, IPCL type II in 29, and IPCL type III in 2. The Kendall rank correlation between pathology and NBI images was significant (p < 0.0001). Conclusions: The dichotomous classification of homogeneous leukoplakia by NBI is meaningful, and endoscopy with the NBI system is a promising tool for the evaluation and management of homogeneous oral leukoplakia.

De novo malignant solitary fibrous tumor of the kidney.

The kidney is a relatively infrequent site for solitary fibrous tumor (SFT). Among the previously reported cases, only two cases of malignant renal SFT developing via dedifferentiation from a pre-existing benign SFT have been reported. Here we reported a case of de novo malignant renal SFT clinically diagnosed as renal cell carcinoma in a 50-year-old woman. The tumor was circumscribed but unencapsulated and showed obvious hemorrhagic necrosis. Microscopically, the tumor was composed of patternless sheets of alternating hypercellular and hypocellular areas of spindle cells displaying mild to moderate nuclear atypia, frequent mitoses up to 8 per 10 high power fields, and a 20% Ki-67 proliferative index. Immunohistochemical studies revealed reactivity for CD34, CD99 and vimentin, with no staining for all other markers, confirming the diagnosis of SFT. No areas of dedifferentiation were seen after extensive sampling. Based on the pathologic and immunohistochemical features, a diagnosis of de novo malignant renal SFT was warranted. Our report expands the spectrum of malignant progression in renal SFTs. Even though this patient has been disease-free for 30 months, long-term follow-up is still mandatory.

Use of endoscopy with narrow-band imaging system in detecting squamous cell carcinoma in oral chronic non-healing ulcers

ObjectivesThis study seeks to analyze the factors associated with the occurrence of squamous cell carcinoma in oral non-healing ulcers for more than 3xa0weeks and investigate the role of endoscopy with narrow-band imaging system (NBI) in detecting carcinoma in these lesions.MethodsThe demographic and clinicopathological data of patients receiving surgical interventions for chronic oral non-healing ulcers, and the intraepithelial papillary capillary loop patterns shown by NBI were retrospectively reviewed and analyzed.ResultsA total of 63 patients (41 males and 22 females) with mean age of 57.9u2009±u200916.7xa0years were enrolled. In univariate analysis, ulcers with induration, history of oral cancer, and intraepithelial microvasculature of NBI were factors associated with the occurrence of squamous cell carcinoma in oral non-healing ulcers. Multivariate analysis showed that the intraepithelial microvasculature of NBI was the only independent factor predicting the occurrence of carcinoma in oral chronic non-healing ulcers with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 93.75xa0%, 91.49xa0%, 78.95xa0%, 97.73xa0%, and 92.06xa0%, respectively.ConclusionsMorphology of intraepithelial microvasculature of NBI, or twisted, elongated, and destructive pattern of intraepithelial papillary capillary loop, is the only independent factor associated with the occurrence of squamous cell carcinoma in oral chronic non-healing ulcers. Endoscope with NBI is a rapid, safe, and promising tool in detecting squamous cell carcinoma in oral chronic non-healing ulcers.

A retrospective review of the prognostic value of ALDH-1, Bmi-1 and Nanog stem cell markers in esophageal squamous cell carcinoma.

Stem cell markers are upregulated in various cancers and have potential as prognostic indicators. The objective of this study was to determine the expression of three stem cell markers, aldehyde dehydrogenase 1 (ALDH-1), B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1), and Nanog, in esophageal squamous cell carcinoma (ESCC) tissues. Immunohistochemistry was used to measure the expression of ALDH-1, Bmi-1, and Nanog in ESCC tissues from 41 patients who received pre-operative chemoradiation. We evaluated the relationship between expression of these markers, and clinicopathological features, tumor regression grade (TRG), and 5-year overall survival (OS). There were no significant associations of ALDH-1 or Bmi-1 expression with age, gender, clinical stage, and treatments (p>0.05). However, patients with Nanog-positive tumors were significantly older than those whose tumors were Nanog-negative (pu200a=u200a0.033). TRG after treatment was significantly associated with expression of ALDH-1 (pu200a=u200a0.001), Bmi-1 (pu200a=u200a0.004), and Nanog (p<0.001). Although OS was significantly better in patients with low TRGs (pu200a=u200a0.001), there were no significant correlations between ALDH-1, Bmi-1, or Nanog with OS. Expression of ALDH-1, Bmi-1, and Nanog correlated with TRG, but not OS. Further large studies are necessary to fully elucidate the prognostic value of these stem cell markers for ESCC patients.

Immunohistochemical study of the Nrf2 pathway in colorectal cancer: Nrf2 expression is closely correlated to Keap1 in the tumor and Bach1 in the normal tissue.

Oxidative stress is a contributing factor in the carcinogenesis of colorectal cancer. The Nrf2 [nuclear factor (erythroid-derived 2)-like 2; NFE2L2] pathway is one of the major cellular defense mechanisms against oxidative stress. This study investigated the expression of the Nrf2 pathway in colorectal cancer. Formalin-fixed paraffin-embedded tissue arrays consisting of the tumor, adjacent normal, and distant normal tissues from the resected specimens of 83 colorectal cancer patients were subjected to immunohistochemical (IHC) staining with antibodies against Nrf2, kelch-like ECH-associated protein 1 (Keap1), p21, P62, Parkinson protein 7 (Park7), prohibitin, BTB and CNC homology 1 (Bach1), CD34 and 8-hydroxy-2′-deoxyguanosine (8-OHdG). The mean IHC density of each IHC staining was digitally analyzed. The results showed that molecules of the Nrf2 pathway were actively expressed, with different expression profiles among the tumor and normal tissues. The oxidative stress, represented by the mean IHC staining density of 8-OHdG, did not differ but was correlated with the expressions of different Nrf2 pathway molecules to a varied extent in tumor and normal tissues of colorectal cancer. Keap1 [estimate, 0.49; 95% confidence interval (CI), 0.19-0.79] and Bach1 (estimate, 0.24; 95% CI, 0.11-0.38) were significant predictors for the expression of 8-OHdG and had the closest proximity to Nrf2 in the cluster dendrogram of the tumor and distant normal tissues, respectively. Advanced stage (estimate, 14.9; 95% CI, 2.99-26.8) and current smoker (estimate, 15.6; 95% CI, 1.92-29.3) were significant predictors with high estimates for Bach1 in the adjacent and distant normal tissues, respectively. In colorectal cancer, the molecules of the Nrf2 pathway have different expression profiles and a difference in their importance, especially Keap1 and Bach1, related to Nrf2 and oxidative stress among tumor and normal tissues.

Dual-colour chromogenic in-situ hybridization is a potential alternative to fluorescence in-situ hybridization in HER2 testing.

Hwang C‐C, Pintye M, Chang L‐C, Chen H‐Y, Yeh K‐Y, Chein H‐P, Lee N & Chen J‐R u2028(2011) Histopathology59, 984–992