Ovarian cancer and late onset paraneoplastic cerebellar degeneration.

Paraneoplastic cerebellar syndrome (PCD) is a rare, neurological disorder that primarily emerges before the detection of malignancy. We present a case involving a 52-year-old woman who was diagnosed and treated for primary ovarian cancer in 2005. In 2007, the patient exhibited ataxia, dysarthria and peripheral neuropathy. Following neurological assessment and immunologic testing, the diagnosis of PCD was made. The disease typically precedes the detection of malignancy by a year or more and has been documented in only a few cases following the treatment for ovarian cancer.

Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis.

PURPOSE: The epidermal growth factor receptor (EGFR) is frequently overexpressed in non-small-cell lung carcinoma (NSCLC), and EGFR inhibitors are promising new therapeutic agents. The molecular mechanisms responsible for EGFR overexpression are poorly understood. MATERIALS AND METHODS: Gene copy number and protein status of EGFR were investigated in microarrayed tumors from 183 NSCLC patients, including squamous cell carcinoma (SCC; 89 patients) and non-SCC (94 patients) histologies. Protein expression was assessed by immunohistochemistry on a scale from 0 to 400 (percentage of positive cells x staining intensity). Gene and chromosome 7 copy numbers were identified by fluorescent in situ hybridization (FISH). RESULTS: EGFR protein overexpression was observed in 62% of the NSCLC (25% scored 201 to 300; 37% scored 301 to 400), more frequently in SCC than non-SCC (82% v 44%; P <.001), and in 80% of the bronchioloalveolar carcinomas. The prevalent FISH patterns were balanced disomy (40%) and trisomy (38%) for EGFR gene and chromosome 7 (40%), whereas balanced polysomy was seen in 13% and gene amplification was seen in 9% of the patients. Gene copy number correlated with protein expression (r = 0.4; P <.001). EGFR overexpression or high gene copy numbers had no significant influence on prognosis. CONCLUSION: EGFR overexpression is frequent in NSCLC, is most prominent in SCC, and correlates with increased gene copy number per cell. High gene copy numbers per cell showed a trend toward poor prognosis. It will be important to evaluate EGFR gene and EGFR protein status and signal protein expression to properly interpret future clinical trials using EGFR inhibitors.

Epidermal growth factor receptor family in lung cancer and premalignancy.

Lung cancer, like many other epithelial malignancies, is thought to be the outcome of genetic and epigenetic changes that result in a constellation of phenotypic abnormalities in bronchial epithelium. These include morphologic epithelial dysplasia, angiogenesis, increased proliferative rate, and changes in expression of cell surface proteins, particularly overexpression of epidermal growth factor receptor (EGFR) family proteins. The EFGR family is a group of four structurally similar tyrosine kinases (EGFR, HER2/neu, ErbB-3, and ErbB-4) that dimerize on binding with a number of ligands, including EGF and transforming growth factor alpha. Epidermal growth factor receptor overexpression is pronounced in virtually all squamous carcinomas and is also found in > or = 65% of large cell and adenocarcinomas. It is not expressed in situ by small cell lung carcinoma. Overexpression of EGFR is one of the earliest and most consistent abnormalities in bronchial epithelium of high-risk smokers. It is present at the stage of basal cell hyperplasia and persists through squamous metaplasia, dysplasia, and carcinoma in situ. Recent studies of the effect of inhibitors of receptor tyrosine kinases suggest that patterns of coexpression of multiple members of the EGFR family could be important in determining response. Intermediate endpoints of such trials could include monitoring of phosphorylation levels in signal transduction molecules downstream of the receptor dimers. These trials represent a new targeted approach to lung cancer treatment and chemoprevention that will require greater attention to molecular endpoints than required in past trials.

HER2/neu expression in malignant lung tumors.

Despite intensive treatment efforts, the prognosis for lung cancer is very poor; less than 15% of patients survive 5 years. Trastuzumab, a monoclonal antibody targeting the HER2/neu protein receptor, is effective in the treatment of metastatic breast cancer and may be useful in the treatment of non-small cell lung cancer (NSCLC). Using the HercepTest (Dako; Carpenteria, CA), 25% of NSCLC show 2+ or greater HER2/neu expression, but only 6% to 8% of NSCLC tumors have 3+ overexpression. Positive HER2/neu expression is most often seen in adenocarcinomas compared with squamous cell carcinomas or large cell carcinomas, and is rarely seen in small cell lung cancer. As determined by fluorescence in situ hybridization analysis, the high degree of HER2/neu gene expression and gene amplification seen in breast cancer is lower in NSCLC. Polysomy is the cause of increased HER2/neu expression in most NSCLC. Prospective clinical studies with trastuzumab in lung cancer are ongoing. Future studies in NSCLC need to include immunohistochemistry and fluorescence in situ hybridization analysis to determine the method of choice for evaluating clinically relevant HER2/neu-positive tumors.

The E-cadherin cell-cell adhesion complex and lung cancer invasion, metastasis, and prognosis.

BACKGROUND: Lung cancer is the most common cause of cancer deaths in the western world. Progress in treatment results has been limited, and the prognosis is poor with a 5-year survival less than 15%. Based on new developments in molecular biology, our knowledge about lung carcinogenesis and mechanisms for invasion and metastasis has expanded and may in the future lead to more specific targeted therapies and better prognosis. The E-cadherin-catenin complex is critical for intercellular adhesiveness and maintenance of normal and malignant tissue architecture. Reduced expression of this complex in malignant disease is associated with tumour invasion, metastasis, and unfavorable prognosis. METHODS: This review is based on search in the Medline database from 1991 to 2001. We have reviewed the relevance of the E-cadherin-catenin adhesion complex in malignancy in general and lung cancer in particular. Furthermore, its role as target for specific therapy is discussed. RESULTS: Available data indicate that alterations of proteins involved in the E-cadherin-catenin complex are early incidents in cancer development. Reduced or altered expression of one or more of the components in this complex is associated with extended invasive and progressive behavior of cancer cells. Consistently, the E-cadherin-catenin complex appears to be increasingly delicate with regard to cancer prognosis. beta-Catenin, one of the components of the adhesion complex, also plays a significant role in cell signal transduction, gene activation, apoptosis inhibition, and increased cellular proliferation and migration. CONCLUSION: Inactivation of the E-cadherin-catenin adhesion complex, induced by genetic and epigenetic events, plays a significant role in multistage carcinogenesis, and seems to be associated with dedifferentiation, local invasion, regional metastasis, and reduced survival in lung cancer.

Urachal carcinoma: key points for the general surgeon.

Urachal carcinoma is a rare neoplasm with the majority of cases reported in the urologic literature. Because of its presentation as an intra-abdominal mass with involvement of adjacent structures the general surgeon may be consulted early in the diagnostic evaluation. One should be aware of this entity as early recognition and appropriate surgery provides the best opportunity for long-term survival. Herein we describe a typical case, appropriate evaluation, and review of the literature.

High-resolution computed tomography features of nonspecific interstitial pneumonia and usual interstitial pneumonia.

OBJECTIVE: To assess the accuracy of high-resolution computed tomography (HRCT) in the diagnosis of nonspecific interstitial pneumonia (NSIP). We hypothesized that the computed tomography (CT) features of NSIP could be distinguished from those of usual interstitial pneumonia (UIP). METHODS: The HRCT images of 47 patients with surgical lung biopsy-proven NSIP (n = 25) and UIP (n = 22) were independently reviewed by 2 thoracic radiologists. Predominant imaging patterns, most likely diagnosis, and diagnostic level of confidence were recorded. A confident HRCT diagnosis of NSIP was based on the presence of spatially uniform, bilateral, basal-predominant ground-glass and/or reticular opacities with little if any honeycombing, whereas UIP was confidently diagnosed if a spatially inhomogeneous, bilateral, peripheral, basal-predominant pattern of reticular opacities and honeycombing with little if any ground-glass attenuation was identified. RESULTS: A predominant pattern of ground-glass and/or reticular opacity with minimal to no honeycombing was demonstrated in 48 (96%) of 50 readings in patients with NSIP. Conversely, the presence of honeycombing as a predominant feature had a predictive value of 90% for UIP (P < 0.001). Usual interstitial pneumonia was more likely than NSIP to be subpleural and patchy (P < 0.001). A confident CT diagnosis of NSIP and UIP was correct in 73% and 88% of cases, respectively. The correctness of a CT diagnosis made at intermediate or high confidence was 68% and 88%, respectively. The kappa value for distinction of NSIP from UIP was 0.72. CONCLUSION: In contrast to previous reports, NSIP can be separated from UIP in most cases. The presence of honeycombing as a predominant imaging finding is highly specific for UIP and can be used to differentiate it from NSIP, particularly when the distribution is patchy and subpleural predominant. The presence of predominant ground-glass and reticular opacity is highly characteristic of NSIP, but there is a subset of patients with UIP who have this pattern and may require biopsy for differentiation from NSIP.