Prognostic and clinical significance of subcellular CDC27 for patients with rectal adenocarcinoma treated with adjuvant chemotherapy.

Rectal adenocarcinoma (READ) constitutes one-third of newly diagnosed colorectal cancer cases. Surgery, chemotherapy and concurrent chemoradiotherapy are the main treatments to improve patient outcomes for READ. However, patients with READ receiving these treatments eventually relapse, leading to a poor survival outcome. The present study collected surgical specimens from patients with READ and determined that cytoplasmic cell division cycle 27 (CDC27) expression was associated with the risk of lymph node metastasis and distant metastasis. Nuclear CDC27 expression was negatively associated with 5-year disease-free survival (DFS) and 5-year overall survival (OS) rates. Multivariate Cox proportional regression analysis showed that nuclear CDC27 was an independent prognostic factor in the patients with READ, especially in those treated with adjuvant chemotherapy. High nuclear CDC27 expression was significantly associated with poorer 5-year DFS (HR, 2.106; 95% CI, 1.275-3.570; P=0.003) and 5-year OS (HR, 2.369; 95% CI, 1.270-4.6810; P=0.005) rates. The data indicated that cytoplasmic CDC27 expression could affect tumor progression and that it plays an important role in metastasis. Nuclear CDC27 expression was markedly associated with poorer survival outcomes and was an independent prognostic factor in patients with postoperative adjuvant chemotherapy-treated READ. Thus, CDC27 expression serves as a potential prognostic marker for rectal tumor progression and chemotherapy treatment.

Remarkable Response to Cisplatin Doublet Chemotherapy in Pulmonary Metastasis With Left Atrial Extension From a Nasopharyngeal Cancer.

A 60-year-old male patient whose nasopharyngeal carcinoma was brought to complete remission with induction chemotherapy composing of cisplatin plus fluorouracil and subsequent radiotherapy with intent of cure eight years ago presented with dyspnea due to left side massive pleural effusion with pleural seedings, left lower lobe huge space occupying lesion, and left atrial tumor extending from the intrapulmonary lesion through left inferior pulmonary veins. Pleural biopsy revealed a picture of nonkeratinizing squamous cell carcinoma positive for Epstein-Barr virus-encoded small RNAs in situ hybridization, leading to a diagnosis of late pulmonary metastases from the antecedent nasopharyngeal carcinoma. Systemic chemotherapy with initial cisplatin plus paclitaxel and subsequent cisplatin plus gemcitabine brought remarkable resolution to the malignant cardiac and intrathoracic lesions. So far as we know, this is the first case report of left atrial invasion from pulmonary metastasis of a nasopharyngeal carcinoma origin in the English literature.

Genetic polymorphism and gene expression of microsomal epoxide hydrolase in non-small cell lung cancer.

Genetic polymorphisms of microsomal epoxide hydrolase (mEH) have been associated with increased risk of lung cancer. However, expression of mEH and its clinical significance in non-small cell lung cancer (NSCLC) have not been investigated. In this study we investigated the expression and genetic polymorphism of mEH in non-small cell lung cancer (NSCLC) patients. Genetic polymorphism was determined by restriction fragment length polymorphism of polymerase chain reaction (PCR) products. The allelic expression pattern as well as expression level of mEH were determined by reverse transcription-PCR (RT-PCR), cDNA sequencing, sequence alignment, immunoblotting and immunohistochemistry. Genotype distributions of mEH in Taiwan's NSCLC patients were 44.4% of 340TAC/340TAC, 48.6% of 340TAC/340CAC, and 7.0% of 340CAC/340CAC in exon 3, and 80.6% of 418CAT/418CAT, 19.4% of 418CAT/418CGT and 0% of 418CGT/418CGT in exon 4. Of the 72 NSCLC biopsies analyzed, mEH was expressed in 60 (83%) surgical specimens, and the major allelic expression pattern was fast type (Tyr113) in exon 3 (90.3%) and slow type (His139) in exon 4 (100%). Immunohistochemical staining showed that mEH was expressed in 326 of 423 (77.0%) tumor (lung tissue) specimens and in 48 of 93 (51.6%) metastatic lymph nodes. A significant difference in patient survival was found when mEH expression and adriamycin-containing chemotherapy were used to group patients (p=0.0167). In conclusion, with the combination of fast type (Tyr113) and slow type (His139), the mEH enzyme expressed in most NSCLC patients may have intermediate activity. Our findings indicate that with respect to cancer risk and disease progression, the expression level of mEH is as important as genetic polymorphism. In addition, mEH expression in NSCLC could be involved in drug resistance and prognosis of patients.

Overexpression of aldo-keto reductase 1C2 as a high-risk factor in bladder cancer.

Intravesical adjuvant chemotherapy and neoadjuvant chemotherapy has been respectively administered for superficial transitional cell carcinoma (TCC) of urinary bladder and advanced TCC for years. However, the therapeutic efficacy is limited. Recently, overexpression of aldo-keto reductase (AKR) in lung, esophageal, uterine cervical and ovarian cancers was shown to be closely associated with disease progression and drug resistance. In this study, we used immunohistochemistry to determine AKR expression in pathological specimens of 347 patients with urinary bladder cancer (UBC). Some of these patients were from areas with a high risk of black foot disease (BFD), a disease that is closely associated with arsenic contamination of drinking water. The presence of AKR was confirmed by immunoblotting, matrix-assisted laser desorption/ ionization time of flight mass spectrometry (MALDI-TOF) and reverse transcription-polymerase chain reaction (RT-PCR). AKR isotype was determined by cDNA sequencing. Our results showed overexpression of AKR1C2 in 226 (65.1%) patients. BFD areas had a higher frequency of patients expressing AKR1C2 in UBC. Among AKR1C2-positive UBC, 148 (65.5%) were invasive, 70 (31.0%) were non-invasive and 8 (3.5%) were carcinoma in situ (CIS). These data indicated that AKR1C2 expression could be significantly associated with cancer invasiveness (p<0.001) and disease progression. Because BFD has been closely related to arsenic ingestion, our results suggested that continual intake of arsenic in drinking water might provoke AKR1C2 expression that could in turn induce drug resistance in UBC, and AKR1C2 could be a tumor marker for UBC.

Infection of human papillomavirus and overexpression of dihydrodiol dehydrogenase in uterine cervical cancer.

OBJECTIVE: To determine the association of human papillomavirus (HPV) infection with the expression of dihydrodiol dehydrogenase (DDH) in uterine cervical cancer (UCC). METHODS: In situ hybridization (ISH) and immunohistochemistry were applied to examine pathological specimens of 145 patients with UCC. RESULTS: By ISH, HPV16/18 DNA was detected in 108 (74.5%) UCC cases. DDH expression determined by immunohistochemistry was detected in 81 (75%) lesions among 108 HPV-positive cases. In contrast, of 37 HPV-negative cases, DDH was only detected in 16 (43.2%) of the lesions. A significant correlation was found between DDH expression and the presence of HPV (P < 0.001), FIGO stage (P = 0.004), lymph node involvement (P < 0.001), as well as patients' survival (P = 0.002). In vitro, DDH expression was also found closely associated with HPV infection, and DDH content was proportional to cell sensitivity for cisplatin and doxorubicin. CONCLUSIONS: HPV infection provokes local inflammation, which can then induce DDH expression and drug resistance in UCC. The detailed biological relationship among HPV infection, expression of DDH and drug resistance, however, remains to be clarified.

Cigarette smoking induces overexpression of hepatocyte growth factor in type II pneumocytes and lung cancer cells.

We examined gene expression of hepatocyte growth factor (HGF) and HGF receptor (HGFR), or product of proto-oncogene c-met (c-met), in smokers and nonsmokers with adenocarcinoma (ADC) by suppression subtractive hybridization and microarray techniques. Expression of HGF and c-met was confirmed by RT-PCR. HGF content in the respective tumor mass and nontumor lung tissue was measured by ELISA. HGF in pathologic samples was localized by immunohistochemistry and in situ hybridization. Our results indicate that overexpression of HGFR was frequently detected in ADC cells, whereas overexpression of HGF was detected in alveolar type II (ATII) cells. Overexpression of HGF was correlated with cigarette smoking and tumor stages. In vitro, HGF expression was evaluated in isolated murine ATII cells and in 12 ADC cell lines, and we found that nicotine activated HGF expression in ATII cells and lung cancer cells.

Expression spectra of matrix metalloproteinases in metastatic non-small cell lung cancer.

By combining suppression subtractive hybridization and microarray to examine gene expressions between metastatic and non-metastatic non-small cell lung cancer (NSCLC), we have identified differential expression spectra of matrix metalloproteinases (MMP). Among MMPs, expressions of MMP-13, -14, -15 and -24 decreased, those of MMP-9, -11, -12, -16, -17, -19 and -23B did not change, and those of MMP-1, -2, -7, -8 and -10 increased dramatically. Overexpressions of MMP-1, -2, -7 and -10 were confirmed by reverse transcription-polymerase chain reaction. In this study we further assessed the clinical significance of MMP-1, -2, -7 and -10. Specimens from 472 patients with completely resected NSCLC were examined by immunohistochemistry. The median follow-up period was 38 months (range, 2-113 months). Overexpression of MMP-1 was observed in 72.9% (n=344) of 472 patients, that of MMP-2 was 77.9% (n=352), MMP-7 63.3% (n=299) and that of MMP-10 was 27.1% (n=128). For patients with lymph node metastasis, MMP-1 and -2 overexpressions were not only independent prognostic factors for unfavorable outcome, but also associated with decreased survival (p=0.0015, and p=0.011 respectively). The present study showed that MMP expression spectrum in NSCLC was heterogeneous: expression of some MMP increased, some unchanged, while some decreased. Therefore, it should be worth determining MMP expression pattern as a regimen reference for NSCLC patients who were scheduled to receive MMP inhibitor, which was class-specific, as adjuvant therapeutic agent.

Recurrent carcinosarcoma of the renal pelvis. Case report.

Carcinosarcoma is a malignancy that occurs very rarely in the renal pelvis; thus, only a very limited number of cases has been documented. These tumors are composed of both carcinomatous and sarcomatous elements. We report here a case of a carcinosarcoma composed of well-differentiated, keratinizing, squamous carcinoma cells and high-grade sarcoma cells. Differently from the cases described so far, this carcinosarcoma of the renal pelvis was characterized by the quick recurrence, following complete surgical resection, as a highly disseminated high-grade sarcoma.