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Philip T Cagle

Publications and source records attributed to Philip T Cagle.

At least 19 recordsLinked to original sources
PubMed2006

Expression of apoptotic nuclei by ultrastructural terminal deoxyribonucleotidyl transferase mediated dUTP nick end labeling and detection of FasL, caspases and PARP protein molecules in cadmium induced acute alveolar cell injury.

Cadmium causes cellular damage but the exact mechanism of apoptosis in cadmium induced acute lung injury is not clear. We investigated the sequential expression of apoptotic nuclei and detected related molecules in tissue of cadmium-induced acute lung injury. Forty Sprague-Dawley rats were sacrificed at days 1, 3, 7 and 10 after intra-tracheal cadmium injection (2.5mg/kg). Light microscopic, ultrastructural terminal deoxyribonucleotidyl transferase mediated dUTP nick end labeling (TUNEL), and Western blot analysis for detection of FasL, Bid, cytochrome c, caspase 3 and PARP were carried out. Apoptosis occurred at day 1, and markedly decreased at days 3, 7 and 10 (11.8, 2.8, 0.9, 0.5%, respectively) determined by light microscopy and TUNEL assay. Ultrastructural TUNEL revealed two patterns of nuclear morphology according to the apoptotic stage. One pattern showed chromatin fragmentation and apoptotic nuclear body formation. The other pattern had bleb formation in the chromatin, budding with projection out to the nuclear membranes, fragmentation, segregation of chromatin clumps and apoptotic body formation. Western blot analysis showed prominent expression of FasL at days 1 and 3. Expression of Bid, cytochrome c and caspase 3 were prominent at day 1 compared to days 3, 7 and 10. PARP cleavage was prominent at day 1. In conclusion, intra-tracheal cadmium injection showed active alveolar cell apoptosis at day 1. Ultrastructural TUNEL showed various expressions according to the apoptotic nuclear stage. These studies suggest that cadmium-induced alveolar cell apoptosis is mediated by FasL and caspase-dependent mitochondrial apoptosis pathways.

Animals↗
PubMed2006

Interpreting the histopathology of chronic cough: a prospective, controlled, comparative study.

HYPOTHESIS: Trauma from chronic coughing produces airway inflammation similar to diseases causing cough. DESIGN: Prospective, cross-sectional, controlled, clinicopathologic correlation study in four groups: group 1, cough from intrapulmonary diseases; group 2, cough from extrapulmonary diseases; group 3, cough that was unexplained; and group 4, nonsmoking, asymptomatic control subjects. METHODS: Patients with chronic cough underwent a standardized workup including endobronchial biopsies before treatment. Causes were determined by a favorable response to therapy. Bronchial biopsy samples from control subjects were obtained from surgical specimens. RESULTS: There were 24 adult subjects (13 women and 11 men) with mean cough duration of 8.6 +/- 7.4 years (+/- SD). Thirteen patients had cough due to a specific disease: intrapulmonary diseases in 5 patients, and extrapulmonary diseases in 8 patients. Eleven patients had unexplained cough. Compared to control subjects, there was minimal-to-moderate chronic inflammation in all coughers (p < or = 0.0004), in group 1 (p < or = 0.039), group 2 (p = 0.061), and group 3 (p < or = 0.025) diseases that were not correlated with cough duration. There was no difference in type of inflammation, cough duration, or smoking history between groups, nor were there histologic differences between subjects with explained causes of cough compared with unexplained cough. CONCLUSIONS: Our findings suggest that airway inflammation associated with chronic cough, assessed on morphologic appearance and inflammatory cell counting in hematoxylin-eosin-prepared samples, may be due to the trauma of coughing, and the inflammation may be similar to that seen with diseases putatively thought to cause chronic cough. Investigators must be cautious when attributing pathogenic importance to observed inflammatory changes in airways of coughing subjects.

Asthma↗
PubMed2006

Pleuropulmonary desmoid tumors: immunohistochemical comparison with solitary fibrous tumors and assessment of beta-catenin and cyclin D1 expression.

CONTEXT: Desmoid tumors arising in the lung and pleura are extremely rare and can resemble other, more common neoplasms native to these sites. Alterations of the adenomatous polyposis coli/beta-catenin pathway have been detected in sporadic desmoid tumors and have been associated with nuclear accumulation of beta-catenin and overexpression of cyclin D1. OBJECTIVE: To analyze the expression of beta-catenin and cyclin D1 in desmoid tumors and solitary fibrous tumors (SFTs), and to compare the utilities of these substances for distinguishing between these entities with those of other, more commonly used stains. DESIGN: Formalin-fixed, paraffin-embedded sections of 4 desmoid tumors (1 pulmonary, 1 pleural, 2 pleural/chest wall), and 5 benign and 6 malignant SFTs of the pleura were immunostained for beta-catenin, cyclin D1, ALK1, CD34, vimentin, desmin, smooth muscle actin, muscle-specific actin, S100, and pancytokeratin. Staining intensity and the percentage of stained tumor cells were assessed semiquantitatively. RESULTS: Diffuse moderate or strong nuclear staining for beta-catenin was found in all desmoid tumors, 4 of 5 benign SFTs, and 2 of 6 malignant SFTs. All cases except 1 benign SFT showed concurrent cytoplasmic staining. Nuclear and cytoplasmic cyclin D1 staining was increased in all groups. The best distinction between desmoid tumors and SFTs was provided by CD34 (desmoid tumors, 0/4; SFTs, 8/11) and smooth muscle actin (desmoid tumors, 4/4; SFTs, 0/11). CONCLUSIONS: Our findings suggest that alterations in the adenomatous polyposis coli/beta-catenin pathway and cyclin D1 dysregulation may contribute to the pathogenesis of pleuropulmonary desmoid tumors and SFTs. CD34 and smooth muscle actin stains are particularly useful for differentiating between pleuropulmonary desmoid tumors and SFTs.

Actins↗
PubMed2006

Expression of renal cell carcinoma-associated markers erythropoietin, CD10, and renal cell carcinoma marker in diffuse malignant mesothelioma and metastatic renal cell carcinoma.

CONTEXT: Metastatic renal cell carcinoma (MRCC) involving the thorax can be difficult to distinguish from diffuse malignant mesothelioma (DMM) using traditional morphologic approaches. Standard panels of immunohistochemical markers are of limited benefit. OBJECTIVE: To investigate several antibodies to renal cell carcinoma-associated proteins for differentiating MRCC from DMM. DESIGN: One hundred DMMs and 20 MRCCs were evaluated for immunoexpression of erythropoietin. The same cases and an additional 45 DMMs were evaluated for CD10 and renal cell carcinoma marker (RCCMa) immunoreactivity. RESULTS: Erythropoietin was expressed in 100% of DMMs and MRCCs. Staining for CD10 was observed in 54% of DMMs and 100% of MRCCs. RCCMa stained 26% of DMMs and 55% of MRCCs. Although erythropoietin staining was similarly strong and diffuse in both DMM and MRC, patterns of staining for RCCMa and CD10 differed between MRCC and DMM. Immunoreactivity was strong and diffuse for both RCCMa and CD10 in most MRCCs. Of CD10-positive DMMs, nearly half showed staining in less than 50% of tumor cells and about one fourth of positive cases exhibited only weak to moderately intense staining. Only half of RCCMa-positive DMMs showed staining in more than 49% of tumor cells and staining was only weak to moderately intense in most cases. CONCLUSIONS: Given the overlap in the expression of renal cell carcinoma markers in MRCC and DMM, results with these markers must be interpreted cautiously and should be used in conjunction with mesothelium-associated markers. Differences in expression may potentially help distinguish MRCC from DMM inasmuch as strong and diffuse expression of RCCMa and CD10 supports a diagnosis of MRCC over DMM.

Biomarkers, Tumor↗
PubMed2005

Distinction of pulmonary small cell carcinoma from poorly differentiated squamous cell carcinoma: an immunohistochemical approach.

Accurate morphologic distinction between small cell carcinoma and poorly differentiated squamous cell carcinoma has critical therapeutic significance, but can be limited by crush artifact, tumor necrosis, limited tumor representation, and overlapping morphologic features. We evaluated a panel of antibodies for their efficacy in distinguishing between these neoplasms. Formalin-fixed paraffin-embedded tissue sections of small cell carcinomas and poorly differentiated squamous cell carcinomas underwent immunohistochemical staining with antibodies to thyroid transcription factor-1, p63, high molecular weight keratin, and p16(INK4A). Of 28 small cell carcinomas, 26 (93%) small cell carcinomas showed diffuse moderate or strong staining for thyroid transcription factor-1 with no staining for high molecular weight keratin and p63. In contrast, 27/28 (96%) poorly differentiated squamous cell carcinomas manifested opposite immunoreactivities, with diffuse moderate or strong staining for high molecular weight keratin and p63, and no or minimal staining for thyroid transcription factor-1. In two additional cases originally interpreted as small cell carcinoma, high molecular weight keratin highlighted small numbers of neoplastic large cells, leading to reclassification as combined small cell and non-small cell carcinomas. p16(INK4A) expression varied widely in poorly differentiated squamous cell carcinomas, but was consistently moderate or strong and diffuse in small cell carcinomas, and proved helpful in the two thyroid transcription factor-1-negative small cell carcinomas. This study demonstrates that a panel consisting of antibodies to thyroid transcription factor-1, p63, high molecular weight keratin, and p16(INK4A) is highly effective for distinguishing between small cell carcinoma and poorly differentiated squamous cell carcinoma. This panel also facilitates diagnosis of combined small cell and non-small cell carcinomas.

Carcinoma, Small Cell↗
PubMed2005

Comparison of monoclonal versus polyclonal calretinin antibodies for immunohistochemical diagnosis of malignant mesothelioma.

Of putative specific markers for diffuse malignant mesothelioma, nuclear staining with Zymed polyclonal calretinin antibody has shown the best specificity to date for epithelial diffuse malignant mesothelioma versus adenocarcinoma. We compared specificity and sensitivity of this polyclonal antibody for diagnosis of diffuse malignant mesothelioma with a new monoclonal antibody from DAKO. One hundred eighteen adenocarcinomas and 111 diffuse malignant mesotheliomas-70 epithelial, 22 sarcomatous, and 19 biphasic-were immunostained with calretinin antibodies from Zymed (polyclonal rabbit, prediluted, PAD:DC8) and DAKO(monoclonal mouse, 1:100, clone DAK Calret 1) using manufacturer-recommended procedures. Cases were blinded and assessed for nuclear versus cytoplasmic staining, percent positive cells, and background. Both antibodies showed similar positive predictive values for diffuse malignant mesothelioma by nuclear staining (Zymed=95%; DAKO=97%). False positives in 4 (3.4%) and 2 (1.7%) adenocarcinomas, respectively, stained greater than 10% of cells. Sensitivity for epithelial malignant mesothelioma was slightly less for DAKO antibody (Zymed=80%; DAKO=73%). Neither antibody performed well on sarcomatous malignant mesothelioma (Zymed=2/22; DAKO=1/22). Both antibodies are useful in the diagnosis of epithelial malignant mesothelioma, although monoclonal antibody is slightly less sensitive.

Antibodies↗
PubMed2005

Localized malignant mesothelioma.

Localized malignant mesotheliomas are uncommon sharply circumscribed tumors of the serosal membranes with the microscopic appearance of diffuse malignant mesothelioma but without any evidence of diffuse spread. Little is known about their behavior. We report 23 new cases. The mean age at presentation was 63 years, and the sex ratio was approximately 2:1 (male/female). Twenty-one tumors were pleural and 2 were peritoneal. Sixteen tumors reproduced microscopic patterns of diffuse epithelial mesotheliomas, 6 had mixed epithelial and sarcomatous patterns, and 1 was purely sarcomatous. After surgical excision of the tumor, 10 of 21 patients with follow-up data were alive without evidence of disease from 18 months to 11 years after diagnosis. Patients who died had developed local recurrences and metastases, but none had diffuse pleural spread. Localized malignant mesotheliomas should be separated from diffuse malignant mesotheliomas because of their localized presentation, quite different biologic behavior, and far better prognosis.

Adult↗
PubMed2005

Silicone thorax due to a ruptured breast implant.

A woman with a history of bilateral mastectomy and silicone implants for fibrocystic disease and a history of atrial septal defect repair presented with pleural nodules on a chest radiograph. A thorascopic biopsy performed for possible mesothelioma demonstrated chronic inflammation and focal pleural fibrosis due to a foreign-body reaction secondary to silicone. This was confirmed using scanning electron microscopy and energy-dispersive radiograph elemental analysis. As the population ages, the increasing frequency of ruptured silicone implants and the need for heart surgery may result in a corresponding increase in the risk for fibrothorax secondary to inadvertent silicone introduction during surgery.

Breast Implants↗
PubMed2005

Prognostic significance of cyclooxygenase 2 expression in 259 cases of non-small cell lung cancer.

CONTEXT: Previous studies report that increased expression of cyclooxygenase 2 (COX-2) correlates with poor clinical outcome in several malignancies, including non- small cell lung carcinoma (NSCLC). Cyclooxygenase 2 inhibitors have been reported to effectively inhibit carcinogenesis in colon cancer experimental models. OBJECTIVE: We examined COX-2 expression in 259 cases of NSCLC to evaluate its prognostic significance. DESIGN: Sections of NSCLC from patients with a median 5-year follow-up were immunostained with COX-2 monoclonal antibody (1:150) using the Dako mouse EnVision;pl system. Extent of COX-2 expression in neoplastic cells was recorded as follows: 0, 0% to 10% of cells positive; 1, 11% to 33% positive; 2, 34% to 66% positive; and 3, more than 66% positive. Intensity was scored as either increased (+) or not increased (-), compared to internal control smooth muscle and endothelial cells. Kaplan-Meier analysis was used to assess the relationship between survival and COX-2 expression, using the log-rank test for statistical significance. RESULTS: No relationship was found between the extent and/or the intensity of COX-2 expression and patient survival when the entire cohort was considered. However, when separately analyzed according to disease stage and intensity of COX-2 expression, a significant relationship (P = .03) between increased COX-2 expression and shortened patient survival was found only in patients with stage I and II NSCLC. CONCLUSIONS: To our knowledge, this is the largest series of NSCLCs in which COX-2 has been investigated as a prognostic marker. The findings in this large series support previous studies of smaller cohorts that reported that increased COX-2 expression predicts poor outcome in patients with early-stage NSCLC.

Biomarkers, Tumor↗
PubMed2005

Differential diagnosis of benign and malignant mesothelial proliferations on pleural biopsies.

CONTEXT: Although much of the pathology literature focuses on differential diagnosis of diffuse malignant mesothelioma from other types of cancer, the primary diagnostic challenge facing the pathologist is often whether a mesothelial proliferation on a pleural biopsy represents a malignancy or a benign reactive hyperplasia. DESIGN: Based on previous medical publications, extensive personal consultations, and experience on the United States-Canadian Mesothelioma Reference Panel and the International Mesothelioma Panel, salient information was determined about interpretation of benign versus malignant mesothelial proliferations on pleural biopsies. RESULTS: Differentiation of benign reactive mesothelial hyperplasia from diffuse malignant mesothelioma is often difficult. Benign reactive mesothelial hyperplasia may mimic many features ordinarily associated with malignancy, and diffuse malignant mesothelioma may be cytologically bland. Entrapment of benign reactive mesothelial cells within organizing pleuritis may mimic tissue invasion. CONCLUSIONS: Various histologic clues favor a benign over a malignant mesothelial proliferation and vice versa. Invasion is the most reliable criterion for determining that a mesothelial proliferation is malignant. When there is any doubt that a pleural biopsy represents a malignancy, we recommend a diagnosis of atypical mesothelial proliferation.

Biopsy↗
PubMed2005

Review and update of uncommon primary pleural tumors: a practical approach to diagnosis.

OBJECTIVE: We address the current classifications and new changes regarding uncommon primary pleural tumors. Primary pleural tumors are divided according to their behavior and are discussed separately as benign tumors, tumors of low malignant potential, and malignant neoplasms. DATA SOURCES: Current literature concerning primary pleural neoplasms was collected and reviewed. STUDY SELECTION: Studies emphasizing clinical, radiological, or pathologic findings of primary pleural neoplasms were obtained. DATA EXTRACTION: Data deemed helpful to the general surgical pathologist when confronted with an uncommon primary pleural tumor was included in this review. DATA SYNTHESIS: Tumors are discussed in 3 broad categories: (1) benign, (2) low malignant potential, and (3) malignant. A practical approach to the diagnosis of these neoplasms in surgical pathology specimens is offered. The differential diagnosis, including metastatic pleural neoplasms, is also briefly addressed. CONCLUSIONS: Uncommon primary pleural neoplasms may mimic each other, as well as mimic metastatic cancers to the pleura and diffuse malignant mesothelioma. Correct diagnosis is important because of different prognosis and treatment implications for the various neoplasms.

Biopsy↗
PubMed2005

Frozen section of lung specimens.

CONTEXT: Frozen section of lung tissue is performed to guide the surgeon in subsequent therapy. DESIGN: Practical experience in frozen section of the lung was reviewed in the medical literature and from the records of several academic hospitals. RESULTS: Most frozen sections of the lung are performed for evaluation of a solitary nodule, a mass, or the surgical margins of a resection. Frozen section may also be used to assess the adequacy of a lung wedge biopsy taken for later diagnosis of a condition. CONCLUSION: The pathologic evaluation of intraoperative pulmonary lesions is indicated for the differential diagnosis of pulmonary nodules and masses, both neoplastic and nonneoplastic, surgical resection margins, and mediastinal lymph nodes. The most worrisome pitfalls involve differentiating benign reactive atypia from malignancy on frozen section.

Diagnosis, Differential↗
PubMed2005

Cytomegalovirus infection masquerading as carcinoma in a lung transplant patient.

In lung transplant patients, most infections produce radiographically diffuse or lobar infiltrates. Solitary nodules suggesting neoplasm may arise in lung transplant patients with lung infections. We describe a 45-year-old woman who underwent bilateral lung transplantation to treat bilateral bronchiectasis and lung fibrosis resulting from Hodgkin disease. Five months later, a solitary mass was identified on chest radiograph in the left upper lobe and left superior mediastinum. Low-power examination of wedge biopsies of the mass showed a florid proliferation of cells with clear to bubbly to eosinophilic cytoplasm and moderate nuclear atypia, proliferating fibroblasts, and necrosis, suggesting a clear cell carcinoma (possibly metastatic renal cell carcinoma). Intranuclear inclusions compatible with cytomegalovirus were identified on high-power examination and confirmed by immunohistochemistry. In lung transplant patients, a cytomegalovirus infection may mimic malignancy both radiographically and on initial histopathologic examination.

Carcinoma↗
PubMed2004

Growth factor independence-1 is expressed in primary human neuroendocrine lung carcinomas and mediates the differentiation of murine pulmonary neuroendocrine cells.

Human small cell lung cancers might be derived from pulmonary cells with a neuroendocrine phenotype. They are driven to proliferate by autocrine and paracrine neuropeptide growth factor stimulation. The molecular basis of the neuroendocrine phenotype of lung carcinomas is relatively unknown. The Achaete-Scute Homologue-1 (ASH1) transcription factor is critically required for the formation of pulmonary neuroendocrine cells and is a marker for human small cell lung cancers. The Drosophila orthologues of ASH1 (Achaete and Scute) and the growth factor independence-1 (GFI1) oncoprotein (Senseless) genetically interact to inhibit Notch signaling and specify fly sensory organ development. Here, we show that GFI1, as with ASH1, is expressed in neuroendocrine lung cancer cell lines and that GFI1 in lung cancer cell lines functions as a DNA-binding transcriptional repressor protein. Forced expression of GFI1 potentiates tumor formation of small-cell lung carcinoma cells. In primary human lung cancer specimens, GFI1 expression strongly correlates with expression of ASH1, the neuroendocrine growth factor gastrin-releasing peptide, and neuroendocrine markers synaptophysin and chromogranin A (P < 0.0000001). GFI1 colocalizes with chromogranin A and calcitonin-gene-related peptide in embryonic and adult murine pulmonary neuroendocrine cells. In addition, mice with a mutation in GFI1 display abnormal development of pulmonary neuroendocrine cells, indicating that GFI1 is important for neuroendocrine differentiation.

Animals↗
PubMed2004

Pulmonary and ophthalmic involvement with Erdheim-Chester disease: a case report and review of the literature.

Erdheim-Chester disease is a rare nonfamilial histiocytic disorder of unknown etiology with characteristic long bone findings. The 3-year survival rate for patients with Erdheim-Chester disease is 50%. Approximately 50% of patients have disease involvement in other tissues, including skin, retro-orbital and periorbital tissues, pituitary-hypothalamic axis, heart, kidney, retroperitoneum, breast, skeletal muscle, and sinonasal mucosa; about 20% of patients have lung involvement. Prognosis generally depends on the extent of the extraosseous disease. For patients with lung involvement, gender distribution is equal, but men typically present at an older age than do women. Approximately 80% of patients present with dyspnea, and most patients have diffuse interstitial infiltrates and pleural and/or interlobar septal thickening on chest radiology. Characteristic lung histopathology includes the accumulation of histiocytes with variable amounts of fibrosis and a variable lymphoplasmacytic infiltrate in a lymphangitic distribution. Immunostains are diagnostically useful, showing immunopositivity for CD68 and factor XIIIa and immunonegativity for CD1a. Birbeck granules are uniformly absent ultrastructurally.

Dyspnea↗
PubMed2004

Transforming growth factor alpha and epidermal growth factor receptor in reactive and malignant mesothelial proliferations.

BACKGROUND: Growth factors such as transforming growth factor alpha (TGF-alpha) and epidermal growth factor receptor (EGFR) play an important role in cell proliferation. The immunohistochemical expression of these factors has been extensively studied in malignant tumors including mesothelioma. However, the comparative expression of these growth factors in mesothelioma and reactive mesothelial proliferations has been less well studied. OBJECTIVE: To evaluate the possible role of TGF-alpha and EGFR in the clinically important distinction between reactive mesothelial proliferations and malignant mesothelioma. METHODS: The expression of TGF-alpha and EGFR was studied in 39 cases of mesothelioma and 30 cases of reactive mesothelial proliferations by means of immunohistochemistry. RESULTS: Fourteen (70%) of 20 reactive mesothelial proliferations tested and 29 (76%) of 38 mesotheliomas tested expressed TGF-alpha. One (3%) of 30 reactive mesothelial proliferations and 17 (45%) of 39 mesotheliomas expressed EGFR. CONCLUSIONS: These results suggest an up-regulation of EGFR in mesothelioma as compared with reactive mesothelial proliferations. This up-regulation further suggests a possible use of EGFR as an adjunct immunohistochemical test in the differential diagnosis of mesothelioma and reactive mesothelial proliferations.

Biomarkers, Tumor↗