Mary Ann Miller

Thyroid transcription factor-1 and cytokeratins 7 and 20 in pulmonary and breast carcinoma.

OBJECTIVE To evaluate the immunohistochemical expression of a lung epithelial gene transcription factor, thyroid transcription factor-1 (TTF-1), in lung and breast carcinoma in pulmonary cytologic preparations and to correlate the results with the expression of cytokeratin 7 (CK7) and 20 (CK20). STUDY DESIGN Cell blocks of cytologic specimens were immunostained with antibodies to TTF-1, CK7 and CK20. Specimens included 41 primary lung carcinomas (21 adenocarcinomas, 8 squamous cell carcinomas and 12 small cell undifferentiated carcinomas) and 6 metastatic breast adenocarcinomas. RESULTS The lung adenocarcinomas showed nuclear reactivity for TTF-1 in 76% (16/21) of the cases and a staining combination of CK7+/CK20- in 95% (20/21) of the cases. Only one case was CK7+/CK20+. All the breast carcinomas were nonreactive to TTF-1, and all were CK7+/CK20-. The squamous cell carcinomas and small cell undifferentiated carcinomas showed TTF-1 positivity in 38% (3/8) and 83% (10/12), respectively.

Alterations in exon 4 of the p53 gene in gastric carcinoma

BACKGROUND & AIMS Our long-term goal was to evaluate the role of p53 in the prognosis of gastric cancer. We previously showed a discrepancy between p53 expression and the presence of mutations when only exons 5-9 were examined. We then evaluated exon 4. METHODS DNA was sequenced from 217 gastric cancers to detect exon 4 alterations. Codon 72 was examined by restriction enzyme digestion. RESULTS Mutations were present in 3.2% of tumors. In addition, 2 polymorphic sites were found at codons 36 and 72. Polymorphisms at codon 36 were only found in 2 patients. In contrast, the codon 72 polymorphism was very frequent. The genotype frequency was arg/arg (54%), arg/pro (33%), and pro/pro (14%). The genotype of the polymorphic site varied with race (P = 0.001): 64% of whites had the arg/arg genotype, compared with 24% of blacks. The difference in genotype by site, sex, or histological tumor type was not statistically significant (P = 0.067). CONCLUSIONS There are several exon 4 alterations in gastric cancers. These include the rare mutations and the very rare codon 36 polymorphism. The most common change is the codon 72 polymorphism, the genotype of which differs significantly with race. The more common arg/arg genotype in whites may explain why whites are more prone to develop cardiac cancer, whereas the more common proline allele in blacks may explain why they are more prone to develop antral cancers. Further studies are required to determine whether the codon 72 polymorphism affects patient predisposition to gastric cancer.

The pattern of cell proliferation in neoplastic and nonneoplastic lesions of ulcerative colitis

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon characterized by repeated episodes of inflammation and epithelial regeneration. Patients with long‐standing UC have an increased risk for the development of dysplasia and subsequent colon carcinoma. Because dysplasia likely results from deregulated cell proliferation, the authors examined Ki‐67 immunoreactivity in tissues from UC patients to examine patterns of proliferation in neoplastic and nonneoplastic lesions.

Centrosome Hyperamplification in Head and Neck Squamous Cell Carcinoma: A Potential Phenotypic Marker of Tumor Aggressiveness†

Objectives/Hypothesis There is currently no single histological or genotypic marker that reliably predicts the biological behavior of head and neck squamous cell carcinoma (HNSCC). While multiple genetic mutations have been investigated, no single genotypic alteration has consistently correlated with tumor aggressiveness. Phenotypic markers may prove more predictive, because they can represent many different genetic alterations. We investigated the frequency of centrosome hyperamplification in HNSCC and examined its usefulness as a marker for tumor recurrence.

Immunolocalization of Transforming Growth Factor α and Epidermal Growth Factor Receptor in Lungs of Patients with Cystic Fibrosis

ABSTRACT Transforming growth factor α (TGF-α) is expressed in respiratory epithelial cells and alveolar macrophages during development and following lung injury. In the present study, the presence and sites of synthesis of TGF-α and its receptor, the epidermal growth factor receptor (EGF-R), were assessed in lung tissue from patients with severe lung disease caused by cystic fibrosis (CF). Lung sections from 24 individuals with CF, obtained at the time of lung transplantation, were compared to lung sections from five lung donors without CF. Cellular sites of TGF-α, EGF-R, and cellular sites of proliferation were assessed by immunohistochemistry. All CF lung sections contained multiple cell types with detectable TGF-α. Compared to control sections, intensity of TGF-α immunostaining in macrophages, airway epithelial cells, and peribronchial submucosal cells was increased. EGF-R was detected in respiratory epithelial and peribronchial stromal cells but not in alveolar macrophages. The intensity of EGF-R staining in CF lung tissue did not differ from that of controls. An increased number of cells expressing Ki-67 nuclear antigen was detected in peribronchial submucosal cells but not bronchiolar epithelial cells in the CF lungs. The increased expression of TGF-α in CF lung tissue supports the concept that TGF-α plays a role in paracrine/autocrine regulation of lung remodeling associated with injury and repair in the lungs of individuals with cystic fibrosis.

Management Implications of Evaluating the N2 and N3 Neck After Organ Preservation Therapy

Objectives/Hypothesis: To determine if metastatic squamous cell carcinoma with proliferative potential persists in N2 and N3 necks after conventional radiation.

Amplification and expression of the cyclin D1 gene in anal and esophageal squamous cell carcinomas

Cyclin D1 is a cell-cycle regulator and candidate proto-oncogene implicated in the pathogenesis of numerous tumor types. Amplification of the cyclin D1 gene occurs commonly in esophageal squamous cell carcinomas. However, no studies have examined the role of cyclin D1 in anal carcinogenesis. We examined 20 esophageal squamous cell carcinomas and 24 anal carcinomas for cyclin D1 alterations. Protein expression was evaluated by immunohistochemistry using the cyclin DIGM antibody (Novocastra, Newcastle upon Tyne, UK). Cyclin D1 amplification was examined by fluorescent in situ hybridization (FISH), using a cyclin D1 probe obtained from Toshiya Inaba at St. Jude Childrens Research Hospital, Memphis, TN. The FISH sections were analyzed using a Leica (Deerfield, IL) confocal microscope. By immunohistochemistry, 75% of esophageal carcinomas showed evidence of cyclin D1 expression. Cyclin D1 amplification was detected by FISH in 65% of esophageal cancers. There was good correlation between cyclin D1 protein expression and gene amplification, although some tumors showed protein overexpression in the absence of gene amplification. Among the 24 anal carcinomas studied, 8% showed weak cyclin D1 immunoreactivity in rare tumor cells. None of the anal tumors showed cyclin D1 amplification. We conclude that cyclin D1 alterations are common in esophageal carcinomas but do not appear to be important in anal carcinogenesis. Immunohistochemical detection of cyclin D1 protein overexpression is a good predictor of cyclin D1 amplification.

Angle calculations for a five-circle diffractometer used for surface X-ray diffraction

The basic equations are derived for the calculation of the angle settings of a five-circle diffractometer used for surface X-ray diffraction. This is done for a specified angle of incidence. An additional constraint that may be imposed is the horizontal alignment of the diffraction rods to match the divergence of the synchrotron X-ray source or the horizontal setting of the physical surface normal. Alignment procedures and the derivation of the orientation matrix are discussed.

Defibrination with Ancrod in Glomerulonephritis: Effects on Clinical and Histologic Findings and on Blood Coagulation

Ancrod, which produces in vivo defibrination, has been shown to improve renal function and decrease fibrin deposition and crescents in experimental glomerulonephritis. Ancrod was given for 14 days to 5 patients with glomerulonephritis, moderate to severe renal functional impairment, crescents, and/or fibrin deposition in glomeruli. 4 patients had systemic lupus erythematosus. Ancrod treatment resulted in fibrinogen levels less than 50 mg/dl without bleeding, decrease of previously elevated factor VIII and von Willebrand factor levels, and normalization of in vitro platelet hyperaggregation. Renal function improved in all 5 patients. Serial renal biopsies showed a relatively rapid decrease of glomerular thrombi and necrosis and little increase in glomerular sclerosis. Ancrod administration appears safe, and may have a role in treatment of certain types of glomerulonephritis.

A unique basal pattern of p53 expression in ulcerative colitis is associated with mutation in the p53 gene

A unique basal pattern of p53 expression in ulcerative colitis is associated with mutation in the p53 gene