The tumour/normal tissue ratio of Keap1 protein is a predictor for lymphovascular invasion in colorectal cancer: a correlation study between the Nrf2 and KRas pathways.

PURPOSE: Oxidative stress has impacts on the KRas and Nrf2/Keap1 pathways, which have multiple interactions with each other and play important roles in colorectal cancer (CRC). This study investigated the expressions of proteins in the KRas and Nrf2/Keap1 pathways and their associations with clinicopathological features in CRC. METHODS: The protein levels of Nrf2, Keap1, Bach1, p62, HO1, KRas, Erk, Raf1 and PI3K in both the tumour and normal tissues of 60 CRC subjects were determined by Western blot and their T/N (tumour/normal tissue) ratios were correlated with clinicopathological features. RESULTS: The T/N ratios of proteins in the KRas and Nrf2/Keap1 pathways had correlation patterns and proximity profiles in cluster dendrograms different in CRC with different status of lymphovascular invasion (LVI) or lymph node/distant metastases. The Keap1 protein T/N ratio was a significant predictor (odd ratio: 2.24; 95% confidence interval: 1.26 - 4.38) of LVI, which in turn predicted metastases (11.0; 3.49 - 39.8). CONCLUSION: The interactions between the KRas and Nrf2/Keap1 pathways may be affected differently by LVI and metastases, and the protein T/N ratio of Keap1 may be helpful for predicting LVI in CRC.

The level of S-glutathionylated protein is a predictor for metastasis in colorectal cancer and correlated with those of Nrf2/Keap1 pathway.

INTRODUCTION: The Nrf2 (nuclear factor erythroid 2-like 2; NFE2L2)/Keap1 (Kelch-like ECH-associated protein 1) pathway and the TXN (thioredoxin)/GSH (glutathione) system interact mutually and regulate cellular redox with impacts on cancer metastasis and S-glutathionylation of protein, which is an indicator of cell distress. This study investigates the levels of proteins in the Nrf2/Keap1 pathway and the TXN/GSH system and SGP (S-glutathionylated protein) in CRC (colorectal cancer) with or without metastasis. MATERIALS AND METHODS: The protein levels of Nrf2, Keap1, Bach1 (BTB domain and CNC homolog 1), TXN, TXNRD1 (thioredoxin reductase 1), GSR (glutathione reductase) and SGP with molecular weight 31-172 kDa in the normal and tumour tissues of 64 CRC subjects were determined by Western blot. RESULTS: The protein levels and their T/N (tumour/normal tissue) ratios of the Nrf2/Keap1 pathway, the TXN/GSH system and SGP were correlated to different extents in the tissues of CRC subjects with or without lymph node/distant metastasis. The T/N ratios of SGP (odd ratio: 0.19; 95% CI: 0.04-0.74) and lympho-vascular invasion (4.2; 1.39-13.73) were significant predictors for metastasis. CONCLUSIONS: SGPs have protein levels correlated with those of the Nrf2/Keap1 pathway and their T/N ratios are a negative predictor for metastasis in CRC.

Oral tongue leukoplakia: analysis of clinicopathological characteristics, treatment outcomes, and factors related to recurrence and malignant transformation.

OBJECTIVES: The tongue is identified as a high-risk site for oral leukoplakia and malignant transformation. The purpose of this study is to investigate the clinicopathological characteristics and treatment outcomes of tongue leukoplakia and assess the factors related to recurrence and malignant transformation. MATERIALS AND METHODS: One hundred and forty-four patients who received carbon dioxide laser surgery for tongue leukoplakia from 2002 to 2019 were analyzed statistically. RESULTS: The follow-up period was 54.90 ± 54.41 months. Thirty patients showed postoperative recurrence (20.83%), and 12 patients developed malignant transformation (8.33%). The annual transformation rate was 2.28%. Univariate analysis showed that a history of head and neck cancer, size of lesion area, clinical appearance, and pathology were significant factors for both recurrence and malignant transformation. In the multivariate logistic regression, a history of head and neck cancer and size of lesion area were independent prognostic factors for recurrence, and a history of head and neck cancer was the only independent factor for postoperative malignant change. CONCLUSIONS: Clinicians should adopt more aggressive strategies for tongue leukoplakia patients with a history of head and neck cancer. CLINICAL RELEVANCE: These results may help clinicians gain a better understanding of oral tongue leukoplakia.

An anatomical perspective on clinicopathological characteristics and treatment outcomes of dorsal and ventrolateral tongue leukoplakia after carbon dioxide laser surgery.

BACKGROUND: The tongue has been identified as a high-risk site for malignant transformation of oral leukoplakia. The purpose of this study was to investigate the clinicopathological characteristics and treatment outcomes of the dorsal and ventrolateral tongue leukoplakia. METHODS: Demographic data and pathological results of patients who underwent carbon dioxide laser surgery for tongue leukoplakia from 2002 to 2019 were retrospectively reviewed and analyzed statistically. RESULTS: Of the 111 patients enrolled, 80 were males and 31 females, with a mean age of 51.86 ± 11.84 years. The follow-up time was 3.74 ± 4.19 years. Fifteen patients had a postoperative recurrence (13.51%). Four (3.6%) patients developed malignant transformation. Annual transformation rate was 4.03%. There were no differences in the time to develop carcinoma (3.19 ± 1.94 vs. 3.51 ± 2.12 years, P = 0.83), overall cumulative malignant transformation rates (7.41% vs. 2.25%, P = 0.12), and annual transformation rates (2.32% vs. 0.64%, P = 0.099). The prevalence of the ventrolateral tongue leukoplakia was higher than that of the dorsal tongue leukoplakia (P < 0.001). The results of multivariate logistic regression analysis showed that the degree of pathology was the only independent prognostic factor related to postoperative malignant transformation (P = 0.045). CONCLUSIONS: Dorsal tongue leukoplakia is not as frequently encountered clinically as ventrolateral tongue leukoplakia. The response of the dorsal tongue and ventrolateral tongue leukoplakia to laser therapy of are comparable in postoperative recurrence and postoperative malignant transformation. Clinicians should take a more aggressive attitude toward oral tongue leukoplakia with higher grade of dysplasia.

Analyzing the influence of gastric intestinal metaplasia on gastric ulcer healing in Helicobacter pylori-infected patients without atrophic gastritis.

BACKGROUND: Gastric epithelial hyper-proliferation was reported in patients with Helicobacter pylori (H. pylori)-infected gastric mucosa with intestinal metaplasia (IM) changes. In patients with gastric ulcer (GU) and IM, the GU may have a different healing rate in comparison to patients without IM. This study aimed to compare the difference in GU healing between H. pylori-infected patients with IM and those without IM. METHODS: We retrospectively analyzed patients at the Keelung Chung Gung Memorial Hospital during the period from March 2005 to January 2011. The inclusion criteria were: 1) endoscopic findings of GU and biopsy histological examination plus rapid urease test indicating H. pylori infection; 2) gastric IM adjacent to a GU but with no atrophic gastritis changes; 3) patients receiving H. pylori eradication triple therapy and 8 weeks of maintenance therapy with a proton pump inhibitor; and 4) patients receiving follow-up endoscopy within the 3rd and the 4th months after treatment. RESULTS: In total, 327 patients with GU and H. pylori infection (136 with IM and 191 without IM) were included. Patients with IM had a higher GU healing rate than those without IM (91.9% vs. 84.3%, P = 0.040). Multivariate logistical regression analysis revealed that failure of H. pylori eradication (Odds = 4.013, 95% CI: 1.840-8.951, P < 0.001) and gastric IM (Odds = 0.369, 95% CI: 0.168-0.812, P = 0.013) were the predictors of non-healing GU following treatment. CONCLUSIONS: Patient with gastric IM change may have a higher GU healing rate than those without gastric IM. However, successful H. pylori eradication is a more important factor for GU healing than gastric IM.

Treatment outcome of vocal cord leukoplakia by transoral laser microsurgery.

The aim of this study is to evaluate the treatment outcome and analyze the associated factors of postoperative recurrence in patients who received transoral laser microsurgery for vocal cord leukoplakia. The demographic, histopathological data were retrospectively reviewed and the factors associated with recurrence of vocal leukoplakia after surgery were analyzed statistically. A total of 44 patients, including 36 males and 8 females, with a mean age of 50.4 ± 13.4 years, were enrolled. All the patients received excision of the vocal leukoplakia by carbon dioxide laser (2-4 Watt, ultrapulse mode) under general anesthesia. No patients had malignant transformation after surgery. Postoperative recurrence occurred in 10 patients (22.7 %). Univariate analysis showed that patients who had the habit of cigarette smoking, alcohol drinking, and presence of gastroesophageal reflux disease tended to recur. Among these risk factors, presence of gastroesophageal reflux disease (odds ratio 8.43) was the independent prognostic factor for recurrence using multivariate logistic regression analysis. Carbon dioxide laser excision is effective for treating vocal leukoplakia that is still confined to dysplasia of any degree, with acceptable morbidity. This study suggests that the presence of gastroesophageal reflux disease is the prognostic indicator for postoperative recurrence of vocal leukoplakia. Aggressive treatment of reflux disease for those who have received surgical excision for vocal leukoplakia is indicated.

Clinical characteristics of narrow-band imaging of oral erythroplakia and its correlation with pathology.

BACKGROUND: To analyze the clinical application of endoscope with narrow-band imaging (NBI) system in detecting high-grade dysplasia, carcinoma in situ, and carcinoma in oral erythroplakia. METHODS: The demographic, histopathological data, and NBI vasculature architectures of patients receiving surgical intervention for oral erythroplakia were retrospectively reviewed and analyzed statistically. RESULTS: A total of 72 patients, including 66 males and 6 females, with mean age of 54.6 ± 11.2 years, were enrolled. The odds ratio of detecting high-grade dysplasia, carcinoma in situ, and carcinoma by twisted elongated morphology and destructive pattern of intraepithelial microvasculature was 15.46 (confidence interval 95%: 3.81-72.84), and the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 80.95%, 78.43%, 60.71%, 90.91%, and 79.17%, respectively, which were significantly better than other two established NBI criteria (p < 0.001). CONCLUSIONS: Twisted, elongated, and destructive patterns of intraepithelial papillary capillary loop of NBI images are indicators for high-grade dysplasia, carcinoma in situ, and invasive carcinoma in oral erythroplakia.

Interleukin-28B gene non-TT allele strongly predicts treatment failure for genotype 1 infected chronic hepatitis C patients with advanced fibrosis: a case control study.

BACKGROUND: The role of single nucleotide polymorphisms (SNPs) of interleukin (IL)-28B in predicting therapeutic response of pegylated interferon (peg-IFN) plus ribavirin (PR) for genotype 1 infected chronic hepatitis C patients with advanced fibrosis (AF) is limited. The aim of this study is to assess its role in predicting sustained virologic responses (SVR) to treatment. METHODS: Forty-two patients with biopsy proven hepatitis C virus (HCV) related AF (group A; Ishak fibrosis score, ≥4) and 126 sex- and HCV genotype-matched patients without AF (group B; Ishak fibrosis score, ≤3) were recruited into study. All patients received PR therapy for 24 weeks. Baseline and on-treatment clinical, virological and host factors were evaluated for treatment efficacy. RESULTS: The SVR rate was significantly lower in group A than group B patients with genotype 1 infection (24% vs. 53.3%; p=0.011). However, it was similar in those with genotype non-1 infection (76.5% vs. 76.5%; p=1.0). IL-28B rs8099917 genotype TT is the strongest predictor for SVR in genotype 1 infection. Patients who had TT genotype and achieved RVR in group A had similar SVR rates with those in group B (44.4% vs. 53.3%; p=0.614). One third of patients in group A developed hematological adverse effects and had required modified doses during antiviral therapy. CONCLUSIONS: In HCV genotype 1 infected AF receiving 24 weeks of PR treatment, patients with IL28B rs8099917 genotype TT, achieving RVR had similar SVR rate with those without AF. In contrast, patients with IL-28B rs8099917 non-TT genotype without achieving RVR are suggested to stop therapy.

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

OBJECTIVES: This study seeks to analyze the factors associated with the occurrence of squamous cell carcinoma in oral non-healing ulcers for more than 3 weeks and investigate the role of endoscopy with narrow-band imaging system (NBI) in detecting carcinoma in these lesions. METHODS: The 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. RESULTS: A total of 63 patients (41 males and 22 females) with mean age of 57.9 ± 16.7 years 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 93.75 %, 91.49 %, 78.95 %, 97.73 %, and 92.06 %, respectively. CONCLUSIONS: Morphology 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 late recurring and easily forgotten tumor: ovarian granulosa cell tumor.

Ovarian granulosa cell tumor (GCT) is a malignant tumor with slow progression. The recurrence of granulosa cell tumor often happens after 5 years, leading to a 'forgotten tumor' by the patient. We present the case of a 64-year-old woman with a presentation of left flank pain. An initial computed tomography scan revealed a single tumor with multiple adjacent organ invasions. Surgical intervention was prescribed and the pathological results revealed a metastatic granulosa cell tumor. We also review the literature for the follow-up and further management of this tumor.

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.

A rare epidermal growth factor receptor (EGFR) gene mutation in small cell lung carcinoma patients.

AIM: Activating mutations in the epidermal growth factor receptor (EGFR) are predominantly detected in pulmonary adenocarcinoma and have been reported in small cell lung cancer (SCLC) for decades. This retrospective single-center study aimed to determine the frequency and types of EGFR mutations in SCLC in Taiwan. METHODS: This study comprises a consecutive cohort of 161 patients histologically diagnosed with SCLC between January 1992 and August 2014 at the Department of Pathology in Keelung Chang Gung Memorial Hospital, Taiwan. Archived formalin-fixed paraffin-embedded sections from 71 patients were eligible for molecular analysis. EGFR mutation analysis was performed using a fully-automated IdyllaTM EGFR Mutation Test and confirmed a comparable result through Qiagen Therascreen® EGFR RGQ PCR. In addition, EGFR gene copy number was assessed in EGFR-mutated tumors by fluorescence in situ hybridization (FISH). RESULTS: Mutational status of the EGFR gene was successfully analyzed in 63 specimens by both IdyllaTM and Qiagen platforms. Both methods detected L858R point mutation in exon 21 in an 81-year-old female and a 47-year-old male non-smoker. Both tumors show no concurrent EGFR gene amplification. The overall agreement between results obtained with the Idylla™ EGFR Mutation Test and Qiagen Therascreen® EGFR RGQ PCR was 100% Conclusions. Our results showed that EGFR mutation is a rare mutation type in a consecutive series of de novo SCLC. Furthermore, the performance of Idylla™ EGFR Mutation Test and Qiagen Therascreen® EGFR RGQ PCR on archived paraffin sections of limited quantities is available with the high agreement of results.

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

AIM: Dual-colour chromogenic in-situ hybridization (dc-CISH) is an emerging methodology for characterizing genomic alterations. This study was aimed at evaluating the performance of a dc-CISH kit (ZytoVision) in determining human epidermal growth factor receptor 2 (HER2) status in breast cancer. METHODS AND RESULTS: Two hundred and twenty-eight invasive breast carcinomas arranged in tissue microarrays were analysed in parallel with dc-CISH, fluorescence in-situ hybridization (FISH), and immunohistochemistry. Of 227 tumours with available FISH and dc-CISH results, HER2 amplification and non-amplification were detected in 49 (21.6%) and 178 (78.4%) tumours, respectively, by both assays. The concordance between dc-CISH and FISH results showed 100% agreement (κ-coefficient=1.00). Immunohistochemically, 162 (71%), 25 (11.0%) and 41 (18%) tumours were scored 0/1+, 2+, and 3+, respectively. The corresponding results with both FISH and dc-CISH demonstrated HER2 amplification in two (3.2%), nine (36%) and 38 (93%) tumours, respectively. Complete consensus among these three methods was observed in 197 cases, representing 98% of all 3+ and 0/1+ tumours (κ-coefficient=0.92). Confirmatory testing of 25 2+ tumours showed complete consensus between FISH and dc-CISH. CONCLUSIONS: dc-CISH is a promising alternative to FISH in HER2 testing, and the single-institute incidence of HER2 amplification in breast cancer in Taiwan is 21.2%.

Comparing the Expressions of Vitamin D Receptor, Cell Proliferation, and Apoptosis in Gastric Mucosa With Gastritis, Intestinal Metaplasia, or Adenocarcinoma Change.

Background: This study aimed to compare the expression of vitamin D receptor (VDR), cell proliferation, and apoptosis in the gastric mucosa of patients with gastritis, intestinal metaplasia (IM), and adenocarcinoma using artificial intelligence. Material and Methods: This study retrospectively enrolled patients at the Keelung Chang Gung Memorial Hospital from November of 2016 to June, 2017, who were diagnosed with gastric adenocarcinoma. The inclusion criteria were patients' pathologic reports that revealed all compartments of Helicobacter pylori infection, gastritis, IM, and adenocarcinoma simultaneously in the same gastric sample. Tissue slides after immunohistochemical (IHC) staining were transformed into digital images using a scanner and counted using computer software (QuPath and ImageJ). IHC staining included PA1-711 antibody for VDR, Ki67 antigen for proliferation, and M30 antibody CK18 for apoptosis. Results: Twenty-nine patients were included in the IHC staining quantitative analysis. The mean age was 69.1 ± 11.3 y/o. Most (25/29, 86.2%) patients had poorly differentiated adenocarcinoma. The mean expression of Ki67 and CK18 increased progressively from gastritis and IM to adenocarcinoma, with statistical significance (P < 0.05). VDR expression did not correlate with Ki67 or CK18 expression. Survival time was only correlated with tumor stage (correlation coefficient = -0.423, P value < 0.05), but was not correlated with the expression of VDR, Ki67, and CK18. Conclusion: Ki67 expression and CK18 expression progressively increased in the areas of gastritis, IM, and adenocarcinoma. No correlation between VDR expression and Ki67 or CK18 expression was found in this study.

A Retrospective Cohort Study of Oral Leukoplakia in Female Patients-Analysis of Risk Factors Related to Treatment Outcomes.

BACKGROUND: The aim of this study was to make a comparison of clinicopathological characteristics of oral leukoplakia between male and female patients following carbon dioxide laser excision for oral leukoplakia and analyze the factors associated with the treatment outcomes in female patients. METHODS: Medical records of patients with oral leukoplakia receiving laser surgery from 2002 to 2020 were retrospectively reviewed and analyzed statistically. RESULTS: A total of 485 patients were enrolled, including 412 male (84.95%) and 73 female (15.05%). Regarding the locations, the predilection site of oral leukoplakia in male patients was buccal mucosa (p = 0.0001) and that for women patients was tongue (p = 0.033). The differences of recurrence and malignant transformation between both sexes were not significant (p > 0.05). Among female patients, area of oral leukoplakia was the risk factor related to recurrence (p < 0.05). Clinical morphology and postoperative recurrence were the risk factors related to malignant transformation (p < 0.05). CONCLUSIONS: In comparison with male patients, there was no significant difference of the postoperative recurrence and malignant transformation of oral leukoplakia in female patients. Among the female patients, clinicians should pay more attention to large-sized and non-homogeneous leukoplakia, and postoperative recurrent lesions.

The Application of High-Dose Proton Pump Inhibitor Induction Treatment before Dual Therapy for Helicobacter pylori Eradication: An Open-Label Random Trial.

This was a prospective, randomized, open-label trial. Patients without previous Helicobacter pylori eradication therapy were randomly assigned to either a high-dose dual therapy (HDDT) group or a traditional clarithromycin/amoxicillin triple therapy (CATT) group. In the HDDT group, patients took rabeprazole, 20 mg, four times per day for three days and then dual therapy with rabeprazole, 20 mg, and amoxicillin, 500 mg, four times per day during the patient's breakfast, lunch, dinner, and bedtime for 14 days. In the CATT group, patients received conventional triple therapy for 14 days (rabeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg twice per day). In the HDDT group, the success rates of H. pylori eradication were 91.7% (95% confidence interval (CI): 0.78-0.97) by intention-to-treat (ITT) and 94.3% (95% CI: 0.79-0.99) by per-protocol (PP) analysis. In the CATT group, the eradication rates were 77.1% (95% CI: 0.61-0.87) by ITT and 84.3% (95% CI: 0.66-0.94) by PP analysis. The study completion rates were 97.2% (35/36) in the HDDT group. Three-day high-dose rabeprazole induction treatment before dual therapy and a schedule of taking the drug at meal and bed times could achieve an acceptable H. pylori eradication rate (>90%) and good drug compliance.

Associations between the Nrf2/Keap1 pathway and mitochondrial functions in colorectal cancer are affected by metastasis.

BACKGROUND: Both mitochondria and the Nrf2/Keap1 pathway are targets of cancer therapy. Reactive oxygen species released from mitochondria can activate Nrf2, and the Nrf2/Keap1 pathway affects glycolysis, oxidative phosphorylation, mitochondrial biogenesis and mitophagy. OBJECTIVE: This study investigates the associations between the expressions of proteins in the Nrf2/Keap1 pathway and those related to mitochondrial function and glycolysis in colorectal cancer (CRC) with or without metastasis. METHODS: The protein levels of HO1, Nrf2, Keap1, Bach1, p21, p62, NRF1, LC3, ATP5B, HSP60 and GAPDH in the normal and tumor tissues of 60 CRC subjects were determined by Western blot. RESULTS: The Keap1 protein levels, the ATP5B/HSP60 ratio and the BEC index were higher in the tumor than in the normal tissues of CRC with or without metastasis. The following clusters were found in the dendrogram: Nrf2 and p21 with ATP5B and GADPH in all the tissues and with NRF1 in all except the tumor tissues with metastasis; Bach1 with ATP5B and GAPDH in the tumor tissues; Keap1 with p62 in all the tissues, with LC3 in the tumor tissues and with NRF1 and HO1 in the tumor tissues with metastasis. CONCLUSIONS: Nrf2, Keap1, Bach1 and p21 have the association with the proteins related to mitochondrial functions different among the tissues of CRC with or without metastasis.

Clincopathological characteristics and treatment outcomes of oral leukoplakia by carbon dioxide laser excision in the elderly patients.

BACKGROUND: Older age is one of the factors associated with malignant transformation of oral leukoplakia (OL). The purpose of this study is to analyze the clincopathological features and treatment outcomes of OL in the elderly patients. METHODS: The demographic data and histopathological results of the patients (age ≥ 65) who received carbon dioxide laser surgery for OL from 2002 to 2017 were analyzed statistically. RESULTS: There were 53 males and 16 females, with a mean age 71.2 ± 4.9. The follow-up time was 42.5 ± 35.2 months. In the univariate analysis, morphology, pathology, and area were found to be factors associated with postoperative recurrence. Among these factors, pathology and area were the independent predictive factors for recurrence in the multivariate logistic regression model. Malignant transformation occurred in 8 of 69 patients (11.6%). CONCLUSIONS: The pathological high-risk dysplasia and area of OL were the two prognostic factors for postoperative recurrence.

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

AIMS: 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). METHODS AND RESULTS: ACD-associated RCC preferentially expressed proximal nephron phenotype (CD10+ /RCC marker+/alpha-methylacyl-CoA racemase+ /glutathione S-transferase-alpha+ /BerEP4+ /cytokeratin 7- /E-cadherin- /high-molecular-weight cytokeratin- /MOC31-). CGH combined with FISH demonstrated non-random chromosomal gains clustering on chromosomes 3 (8/9), 7 (6/9), 16 (7/9), 17 (4/9) and Y (5/9). Chromosomal losses were uncommon. The chromosomal aberrations in all multifocal tumours were not identical for the same kidney or for the same patient, indicating a 'field effect' that induces multiple independent clones. CONCLUSIONS: Although the genetic profiles of ACD-associated RCC showed some similarity to those of papillary RCC, ACD-associated RCC distinctly revealed frequent gains on chromosomes 3 and Y. ACD-associated RCC is characterized not only by its particular clinical setting and histology, but also by its unique immunohistochemical and molecular genetic profiles.