GREM1 is expressed in the cancer-associated myofibroblasts of basal cell carcinomas.

Cancer-associated fibroblasts (CAFs) play important roles in cancer progression through their complex interactions with cancer cells. The secreted bone morphogenetic protein antagonist, gremlin1 (GREM1) is expressed by the CAFs of basal cell carcinomas (BCCs), and promotes the growth of cancer cells. In this study, we investigated the expression of GREM1 mRNAs in various benign and malignant skin tumors, including various BCC subtypes. Analysis by RNA in situ hybridization (ISH) revealed that fibroblasts in the scar tissue expressed GREM1 and α-smooth muscle actin (α-SMA), whereas resident fibroblasts in the dermis of the normal skin did not express GREM1. Real-time polymerase chain reaction analysis showed significantly higher GREM1 expression in skin cancers and pilomatricomas (PMCs) than in other benign skin tumors. Tissue microarrays analyzed by RNA ISH for GREM1 expression also demonstrated that 23% of BCCs, 42% of squamous cell carcinomas, 20% of melanomas, and 90% of PMCs were positive for GREM1 expression, whereas trichoepitheliomas, eccrine poromas, hidradenomas, and spiradenomas were negative for GREM1 expression. Most BCCs that were GREM1 expression positive were of desmoplastic or mixed subtypes, and GREM1 expression was localized to activated myofibroblasts at the tumoral-stromal interface. Interestingly, most PMCs harbored GREM1-expressing fibroblasts, probably because of the inflammatory responses caused by foreign body reactions to keratin. Additionally, in BCCs, stromal GREM1 expression had a strong correlation with CD10 expression. In conclusion, GREM1 is frequently expressed by myofibroblasts in scars or in the stroma of basal cell carcinomas, suggesting that GREM1 expression can be a marker for activated myofibroblasts in the cancer stroma or in scar tissue.

Aurora Kinase A Is a Prognostic Marker in Colorectal Adenocarcinoma.

BACKGROUND: Aurora kinase A (AURKA), or STK15/BTAK, is a member of the serine/threonine kinase family and plays important roles in mitosis and chromosome stability. This study investigated the clinical significance of AURKA expression in colorectal cancer patients in Korea. METHODS: AURKA protein expression was evaluated by immunohistochemistry in 151 patients with colorectal adenocarcinoma using tissue microarray blocks. We analyzed the relationship between clinicopathological characteristics and AURKA expression. In addition, the prognostic significance of various clinicopathological data for progression-free survival (PFS) was assessed. Also we evaluated copy number variations by array comparative genomic hybridization and AURKA gene amplification using fluorescence in situ hybridization in colorectal carcinoma tissues. RESULTS: AURKA gene amplification was found more frequently in the 20q13.2-13.33 gain-positive group than the group with no significant gain on the AURKA-containing locus. AURKA protein expression was detected in 45% of the cases (68/151). Positive staining for AURKA was observed more often in male patients (p = .035) and distally located tumors (p = .021). PFS was shorter in patients with AURKA expression compared to those with low-level AURKA expression (p < .001). Univariate analysis revealed that AURKA expression (p = .001), age (p = .034), lymphatic invasion (p = .001), perineural invasion (p = .002), and TNM stage (p = .013) significantly affected PFS. In a multivariate analysis of PFS, a Cox proportional hazard model confirmed that AURKA expression was an independent and significant prognostic factor in colorectal adenocarcinoma (hazard ratio, 3.944; p < .001). CONCLUSIONS: AURKA could serve as an independent factor to predict a poor prognosis in Korean colorectal adenocarcinoma patients.

Ectopic Pancreas Presenting as a Solid Mediastinal Mass.

Ectopic pancreas is a well-known developmental anomaly found in approximately 2% of all autopsies, frequently in the gastrointestinal tract. Mediastinal pancreatic ectopia is very rare; only a few cases have been described in the English-language literature. According to previous reports, the pancreatic tissue is detected in the cyst wall or appears as small solid components of cystic masses within the anterior mediastinum. In this report, we present a case of ectopic pancreas appearing as a large solid mass in the anterior mediastinum of a 17-year-old male patient.

Primary anaplastic large cell lymphoma of the lung presenting with acute atelectasis.

Non-Hodgkin lymphoma only rarely occurs as a primary lung mass. We report a very rare case of primary pulmonary anaplastic large cell lymphoma presenting with acute atelectasis in a 55-year-old man. Chest computed tomography revealed a consolidated central mass in the left lung with obstructive pneumonia that had developed into total atelectasis. After a bronchoscopic examination failed to yield a definite diagnosis, supraclavicular lymph node biopsy was performed, revealing an anaplastic large cell lymphoma. This case illustrates the need for rapidly locating a possible biopsy site, other than the primary lung mass itself, and the value of empirical steroid treatment for avoiding devastating exacerbation when aggressive pulmonary lymphoma is suspected.

Utility of napsin A and thyroid transcription factor 1 in differentiating metastatic pulmonary from non-pulmonary adenocarcinoma in pleural effusion.

OBJECTIVE: It was our aim to evaluate the usefulness of napsin A and thyroid transcription factor 1 (TTF-1) in the differential diagnosis of metastatic pulmonary and non-pulmonary adenocarcinomas (ACs) in pleural effusion. STUDY DESIGN: A total of 84 pleural effusion fluid cell blocks were collected from metastatic ACs. There were 53 pulmonary ACs and 31 non-pulmonary ACs. Immunohistochemical staining was performed with antibodies against napsin A and TTF-1. RESULTS: Napsin A was positive in 44/53 (83%) cases of pulmonary ACs, and TTF-1 was positive in 30/53 (57%) cases of pulmonary ACs. All non-pulmonary ACs were negative for napsin A and TTF-1. Napsin A showed a reactivity in >75% of the tumor cells in 36 of the 44 positive cases (82%), whereas TTF-1 showed a reactivity in >75% of the tumor cells only in 6 of the 30 positive cases (20%; p < 0.01). Poorly differentiated pulmonary ACs expressed napsin A (73%) more frequently than TTF-1 (53%), but this was not statistically significant (p = 0.45). CONCLUSION: We conclude that napsin A is superior to TTF-1 with regard to distinguishing between metastatic pulmonary and non-pulmonary ACs in cell blocks prepared from malignant pleural effusions.

Expression of E-cadherin, P-cadherin and N-cadherin in oral squamous cell carcinoma: correlation with the clinicopathologic features and patient outcome.

PURPOSE: Alteration of cadherin expression is associated with the loss of cellular differentiation, the acquisition of an invasive phenotype and a poor prognosis in many types of cancer. This study aimed to evaluate the immunoreactivity of E-, P- and N-cadherins (cad) in oral squamous cell carcinoma and to correlate their expression with clinicopathological features and clinical outcome. The interaction between the cadherins was also investigated. METHODS: A total of 71 tissue samples were examined by immunohistochemical methods on paraffin sections using specific antibodies. RESULTS: In the primary lesions and lymph node metastases, the immunoreactivity of E-cad was reduced and P-cad was over-expressed, but the expression of N-cad was negative (p<0.001, 0.01 and 0.05, respectively). The reduced primary E-cad expression was related to the invasion pattern and lymph node metastasis (p=0.046 and 0.037, respectively). However, the expression of cadherins did not appear to differ significantly in relation to the histological grade, invasion, tumour size, stage of oral SCC or tumour recurrence. A much greater reduction in the expression of E-cad was found in the positive N-cadherin group (p=0.008). Nonetheless, cadherin expression was not significantly associated with failure-free survival or overall survival in this experiment subset. CONCLUSION: The reduced E-cad expression and the aberrant N-cad expression are closely associated with each other in oral cancer cases, and this suggests that cadherin switching from E. cad to N. cad may play a critical role in cancer development and metastasis.

Somatic mutations of the beta-TrCP gene in gastric cancer.

Beta-TrCP is a component of the ubiquitin ligase complex targeting beta-catenin for proteasomal degradation, and is a negative regulator of Wnt/beta-catenin signaling. To determine whether genetic alterations of the beta-TrCP gene are involved in the development or progression of gastric cancer, we analyzed its somatic mutations in 95 gastric cancers by single-strand conformational polymorphism and sequencing. We found five missense mutations (5.3%): A99V, H342Y, H425Y, C206Y, and G260E. Tissue carrying mutations showed moderate to strong cytoplasmic and/or nuclear staining of beta-catenin by immunohistochemistry. Thus, somatic mutations of the beta-TrCP gene may contribute to the development of gastric cancer through beta-catenin stabilization.

Pulmonary arterial aneurysms in primary antiphospholipid antibody syndrome.

A 20-year-old man with rapid refractory pulmonary infiltrates, fever, and chill was admitted to our hospital. Microscopic examination showed focal necrosis of the lung tissue, arterial thromboembolism, and alveolar hemorrhage. He tested positive for anticardiolipin IgG antibodies. Because of the absence of underlying diseases, the possibility of secondary antiphospholipid antibody syndrome was excluded. Follow-up chest CT after 2 years revealed pulmonary arterial aneurysms with diffuse ground-glass opacities. The aneurysms were occluded by coil embolization.

Alterations of Fas-pathway genes associated with nodal metastasis in non-small cell lung cancer.

Many types of cancer cells are resistant to Fas-mediated apoptosis by several mechanisms, including the mutations of the genes involved in Fas-mediated apoptosis. In this study, to explore the possibility that the mutations of the genes involved in the proximal pathway of Fas-mediated apoptosis (Fas, FADD, caspase 8 and caspase 10) are involved in cancer metastasis, we have analysed somatic mutation and deletion of these genes in 80 non-small cell lung cancers (NSCLCs) with (n=43) and without (n=37) metastasis to the regional lymph nodes. We found 12 mutations (four Fas, four FADD, and four caspase 10 mutations) in 11 of 80 NSCLCs (13.8%). Interestingly, of these mutations, most mutations (10 out of 12) were detected in the NSCLCs with metastasis, and the frequency in the metastasis lesions (23%) was higher than that in the primary lesions of the NSCLCs without metastasis (5.4%). Furthermore, transfection study revealed that the tumor-derived mutants have decreased apoptosis inductions compared to the wild types. These data suggest that the inactivating mutations of the genes in the proximal pathway of Fas-mediated apoptosis may lead to a decreased cancer cell death and play a role in the metastasis of NSCLC.