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William D Travis

Publications and source records attributed to William D Travis.

At least 19 recordsLinked to original sources
PubMed2026

IASLC Update on Classification of Pulmonary Neuroendocrine Neoplasms.

Since the publication of the 2021 WHO classification of thoracic tumors, our knowledge of pulmonary neuroendocrine neoplasms (NENs) has expanded significantly, particularly through the elucidation of molecular pathways and proposals to refine histopathologic classification. This expanded knowledge across all aspects of pulmonary NENs holds promise for more precise stratification of neuroendocrine tumors (NETs) and the potential development of novel, subtype-specific therapeutic strategies for all NENs. Based on our comprehensive review of the current pulmonary NEN landscape, our multidisciplinary expert panel has deliberated on the modification and updating of the 2021 classification, resulting in the proposal of a new pulmonary carcinoid/NET classification presented in this position paper, which incorporates the following three major points: (1) The proposed framework continues the shift from the traditional carcinoid terminology toward broader adoption of the "NET" nomenclature as found in other organ systems while retaining the term "carcinoid" as the primary diagnostic term to ensure clear communication with thoracic clinical providers. (2) Ki-67 has been incorporated as a diagnostic criterion, aligning with practices in other NET classifications. (3) There is formal recognition of the concept of "carcinoid/NET G3," a rare subset of lung carcinoids characterized by increased proliferative activity but with molecular features more aligned with pulmonary NETs than with high-grade neuroendocrine carcinomas. This position paper on the current knowledge of pulmonary NENs, including the proposed carcinoid/NET classification, will aid in accurate tumor categorization and guide treatment strategies.

Carcinoid tumor↗
PubMed2025

Panorama of Chromosomal Instability in Lung Cancer.

Lung cancer is a highly heterogeneous disease primarily driven by tobacco smoking. About 20% of lung cancers occur among patients who have never smoked (LCINS) with differences in patient ancestry, sex, tumor histology, and clinical features. Our understanding of chromosomal instability in lung cancer, especially LCINS, is still limited. Here, we perform a comprehensive study of 182,429 somatic structural variations (SVs) detected in 1,209 whole-genome sequenced lung cancers, of which 864 LCINS. SVs are more abundant in tumors from patients who have smoked (LCSS); however, they are more complex and play more important roles in tumorigenesis in LCINS. EGFR mutations and KRAS mutations profoundly and independently shape the SV landscape. EGFR-mutant tumors have higher SV burden and more cancer-driving SVs. In contrast, KRAS mutations are associated with lower SV burden and less driver SVs. We decompose 16 SV signatures for both complex and simple SVs that likely represent divergent molecular mechanisms. The SV breakpoints have distinct distributions across the genome depending on the signatures due to mutagenic mechanisms and positive selection. Many established cancer-driving genes are recurrently rearranged by multiple SV signatures suggesting functional convergence of these genome instability mechanisms.

Journal Article↗
PubMed2025

A prognostic signature for lung adenocarcinoma in people who have never smoked.

Knowledge of tumor cell dynamics can inform prognosis and treatment yet is largely lacking for lung adenocarcinoma in people who have never smoked (NS-LUAD). With RNA-seq data from 684 NS-LUAD and validation in an independent dataset, we identified three subtypes with distinct phenotypic traits and cell compositions. Additional genomic and histological data further characterized the subtypes. 'Steady', marked by low proliferation, high alveolar cell fraction, moderate-to-well differentiation, and fewer driver genes' alterations, is linked to prolonged survival and low immune evasion. 'Proliferative' shows high proliferation markers, TP53 mutations, and gene fusions. 'Chaotic', with high epithelial-to-mesenchymal transition markers, has the worst prognosis even within stage I tumors. Lacking known molecular or histological characteristics, this aggressive subtype is solely identified by transcriptomic data. A 60-gene signature recapitulates the overall classification and strongly predicts survival even within subgroups based on tumor stage or known genomic features, emphasizing its potential for improving NS-LUAD prognostication in clinical settings.

Journal Article↗
PubMed2006

Desmoglein 3 as a prognostic factor in lung cancer.

Desmoglein 3 is a desmosomal protein of the cadherin family. Our cDNA expression profile demonstrated that desmoglein 3 was highly expressed in squamous cell carcinoma of the lung but not detected in pulmonary adenocarcinoma or normal lung. To investigate the clinical significance of desmoglein 3 in lung cancer, we surveyed its expression in primary non-small-cell lung cancers and neuroendocrine tumors. We used immunohistochemical analysis to examine the expression of desmoglein 3 by using tissue microarrays containing samples from 300 surgical non-small-cell lung cancer and 183 lung neuroendocrine tumor. Staining status was determined based on the sum of the distribution score (0, 1, or 2) and the intensity score (0, 1, 2, or 3) of the staining signal. Follow-up was available for 346 cases (median follow-up of 2.8 years). We determined the survival statistical significance of desmoglein 3 by using the log-rank test, and we plotted Kaplan-Meier curves. Negative immunohistochemical staining with desmoglein 3 was associated with shorter survival for all lung cancer patients regardless of the histologic subtype (5-year survival of 20.9% versus 49.5%, P < .001) in our series. In patients with atypical carcinoid tumors, lacking desmoglein 3 expression showed a 5-year survival of 0% compared with 36.8% for desmoglein 3-positive cases (P < .001). Desmoglein 3 status indicated a poor prognosis in lung cancers and portends a more aggressive behavior for atypical carcinoid tumors.

Adenocarcinoma↗
PubMed2006

Telomere length, telomerase activity, and expressions of human telomerase mRNA component (hTERC) and human telomerase reverse transcriptase (hTERT) mRNA in pulmonary neuroendocrine tumors.

BACKGROUND: Telomeres are important for chromosome structure and function, protecting them against degradation. However, few studies have examined telomeres in pulmonary neuroendocrine (NE) tumors. METHODS: We investigated deparaffinized sections obtained from 70 primary NE lung tumors [34 typical carcinoids (TCs), 10 atypical carcinoids (ACs), 16 large cell neuroendocrine carcinoma (LCNECs) and 10 small cell lung carcinomas (SCLCs)]. RESULTS: Positive expressions of human telomerase mRNA component (hTERC) and human telomerase reverse transcriptase (hTERT) mRNA were recognized, respectively, in 58% and 74% of TCs, and in 100% and 100% of ACs, LCNECs and SCLCs. Alteration of telomere length was greater in both LCNECs and SCLCs than in TCs. Telomerase activity was detected in LCNECs, but not in TCs. By the reverse-transcriptase polymerase chain reaction (RT-PCR), hTERC mRNA was detected in 100% of LCNECs and TCs examined, while hTERT mRNA was detected in 67% of LCNECs, but not at all in TCs. CONCLUSIONS: These results suggest that alterations in telomere length, telomerase activity, and the expression of hTERT mRNA may (i) play roles in pathogenesis in pulmonary neuroendocrine tumors, and (ii) be a useful tool for differential diagnosis between TCs and LCNECs.

Carcinoma, Neuroendocrine↗
PubMed2006

Intractable desquamative interstitial pneumonia in a tattooed man.

A 20-year-old man with a 15 pack-year history of cigarette smoking had a tattoo outlined on his back with blue pigment. He noticed a dry cough and shortness of breath on exertion when the pigment of other colors was added at the age of 27. He visited our hospital two years later because of severe dyspnea. He was diagnosed with desquamative interstitial pneumonia by surgical lung biopsy. Steroid therapy with cessation of smoking was partially effective, however his disease worsened again and he died three and a half years after the diagnosis because of respiratory failure.

Adult↗
PubMed2006

Idiopathic pulmonary fibrosis: prognostic value of changes in physiology and six-minute-walk test.

RATIONALE AND HYPOTHESIS: Idiopathic pulmonary fibrosis is a fatal disease with a variable rate of progression. We hypothesized that changes in distance walked and quantity of desaturation during a six-minute-walk test (6MWT) would add prognostic information to changes in FVC or diffusing capacity for carbon monoxide. METHODS: One hundred ninety-seven patients with idiopathic pulmonary fibrosis were evaluated. Desaturation during the 6MWT was associated with increased mortality even if a threshold of 88% was not reached. Baseline walk distance predicted subsequent walk distance but was not a reliable predictor of subsequent mortality in multivariate survival models. The predictive ability of serial changes in physiology varied when patients were stratified by the presence/absence of desaturation < or = 88% during a baseline 6MWT. For patients with a baseline saturation < or = 88% during a 6MWT, the strongest observed predictor of mortality was serial change in diffusing capacity for carbon monoxide. For patients with saturation > 88% during their baseline walk test, serial decreases in FVC and increases in desaturation area significantly predicted subsequent mortality, whereas decreases in walk distance and in diffusing capacity for carbon monoxide displayed less consistent statistical evidence of increasing mortality in our patients. CONCLUSION: These data highlight the importance of stratifying patients by degree of desaturation during a 6MWT before attributing prognostic value to serial changes in other physiologic variables.

Aged↗
PubMed2006

Pathologic findings of lung tumors diagnosed on baseline CT screening.

Sixty-five people had a resection of their baseline screen-diagnosed lung cancers in the Early Lung Cancer Action Program. Forty-nine of the carcinomas were solitary, and 42 of these were adenocarcinomas. More than 1 carcinoma was found in 16 patients after pathologic examination of the lobectomy specimen; 15 of the 16 second carcinomas were adenocarcinomas, mixed subtype. Eighteen cases were submitted by local pathologists as Bronchioloalveolar carcinomas but were found to be invasive adenocarcinomas according to the World Health Organization classification by the Pathology Review Panel. Of the 65 resected cases, 57 were N0, 7 were N1, and 1 was N2. Upon careful review of the lobectomy specimens, 49 cases had solitary malignancies, 30 were Stage IA, 13 Stage IB, 3 Stage IIA, 2 Stage IIB, and 1 Stage IIIA on the basis of the American Joint Committee on Cancer/International Union for Cancer Control criteria. In the 16 cases found to have multiple malignancies, 6 had histologically different carcinomas and the remaining 10 had histologically identical malignancies. Eighty-three percent (76/92) of the carcinomas invaded the stroma with destruction of normal lung, and 21% (19/92) also showed either pleural or angiolymphatic invasion, even though 88% (57/65) of the carcinomas were free of lymph node metastases. This report describes the pathologic findings of the resected cases. Histopathologic distinctions among atypical adenomatous hyperplasia, bronchioloalveolar carcinomas, and invasive adenocarcinoma are described in detail.

Aged↗
PubMed2006

Pulmonary microcystic fibromyxoma: Report of 3 cases.

Three cases of pulmonary myxoid tumors showing a variable degree of microcystic change are described. They are presented as incidental solitary peripheral lung nodules on routine radiologic studies. The patients included 2 women, 45 and 65 years old, and 1 man, 33 years old. Clinical work-up showed no evidence of neoplasia in other sites. Following surgical resection, no evidence of disease was observed after a mean follow-up of 48 months. The tumors ranged in size from 1 to 2.3 cm (mean 1.4 cm). Microscopically, the lesions were well circumscribed with conspicuous cystic change and myxoid stroma. Innocuous, widely-spaced, spindled to stellate tumor cells showed minimal nuclear pleomorphism and absence of mitotic activity. The myxoid stroma contained acid mucopolysaccharides, sensitive to hyaluronidase digestion. No epithelial, chondroid, neural, myofibroblastic, lipomatous or vascular differentiation was evident on immunohistochemical studies. Although these cases display cytologic features, myxoid stroma and benign clinical course characteristic of pulmonary myxomas; the presence of microcystic architecture is unique to the current series, and thus a descriptive designation "microcystic fibromyxoma" is suggested.

Adult↗
PubMed2006

Critical roles of capillary endothelial cells for alveolar remodeling in nonspecific and usual interstitial pneumonias.

To characterize the relationship between angiogenesis factors and alveolar remodeling in interstitial lung diseases, we examined alveolar capillary endothelial cells in the normal lung (n=5) and in lungs with nonspecific interstitial pneumonia (NSIP) (n=4) or usual interstitial pneumonia (UIP) (n=6) using immunofluorescence staining for thrombmodulin and von Willebrand factor (vWF). With three-dimensional images of alveolar capillaries, the diameter of capillary tubes and their branching frequency per unit length were determined to define rearrangement of the capillary meshwork. Alveolar capillary endothelial cells in normal lungs expressed surface thrombomodulin, and those in lungs with cellular NSIP often showed coexpression of surface thrombmodulin and cytoplasmic vWF. In the alveolar septa of fibrotic NSIP and UIP, capillary endothelial cells demonstrated vWF in only the cytoplasm. Capillary branching frequencies in NSIP and UIP were decreased to 45% and 22%, respectively, of the normal level (p<0.002). Compared with normal lungs, in NSIP and UIP lungs alveolar capillaries containing TUNEL-positive endothelial cells (p<0.05) showed increases of 3.6-fold and 4.3-fold, respectively, indicating a close correlation between endothelial cell apoptosis and remodeling of alveolar capillary frameworks. The analysis of mRNA expression of vascular endothelial growth factors (VEGF) and their receptors (VEGFR1 and VEGFR2) showed a significant decrease in each VEGF isoform and in VEGFR2 mRNA in representative alveolar wall tissues microdissected from the normal, NSIP, and UIP lungs. These results suggest that decreased expression of VEGF mRNA is associated with a reduction in the number of capillary tubes via endothelial cell apoptosis that possibly results in alveolar remodeling in NSIP and UIP. However, whether VEGF is related to fibroblastic activation in the interstitial matrix remains unclear.

Antigens↗
PubMed2006

Pulmonary neuroendocrine tumors: What (little) do we know?

Pulmonary neuroendocrine tumors are a distinct subset of tumors composing approximately 20% of all lung cancers. The major categories of pulmonary neuroendocrine tumors include typical and atypical carcinoids, large cell neuroendocrine carcinoma, and the more common small cell lung cancer. They are classified into different categories in the 2004 World Health Organization system, but share structural and morphologic features. Despite these shared features, their clinical characteristics range from indolent to aggressive, and therefore the approach to treatment depends on the histologic subtype. This article discusses the current understanding of the epidemiology, pathologic characteristics, treatment, and prognosis of this spectrum of diseases.

Humans↗
PubMed2005

Evaluation of two phosphorylation sites improves the prognostic significance of Akt activation in non-small-cell lung cancer tumors.

PURPOSE: Akt is a serine/threonine kinase that has been implicated in lung tumorigenesis and lung cancer therapeutic resistance. Full activation of Akt requires two phosphorylation events, but only one site of phosphorylation (S473) has been evaluated thus far in clinical non-small-cell lung cancer (NSCLC) specimens, which has resulted in conflicting results regarding the prognostic significance of Akt activation in NSCLC. In this study, we sought to determine whether evaluation of Akt phosphorylation at T308 would improve prognostic accuracy. PATIENTS AND METHODS: Phosphospecific antibodies against T308 and S473 were validated and used in an immunohistochemical analysis of tissue microarray slides containing NSCLC specimens (n = 300) and surrounding lung tissue specimens (n = 100). RESULTS: Phosphorylation of either S473 or T308 was positive in most NSCSLC specimens, but was detected rarely in surrounding normal tissues. When Akt activation was defined by using both sites of phosphorylation, Akt activation was specific for NSCLC tumors versus surrounding tissue (73.4% v 0%; P < .05), was higher in adenocarcinoma than in squamous cell carcinoma (78.1% v 68.5%; P = .040), and was associated with shorter overall survival for all stages of disease (log-rank P = .041). In multivariate analyses, increased phosphorylation of T308 alone was a poor prognostic factor for stage I patients or for tumors < 5 cm (log-rank P = .011 and P = .015, respectively). CONCLUSION: These results suggest that monitoring phosphorylation of Akt at T308 improves the assessment of Akt activation, and show that Akt activation is a poor prognostic factor for all stages of NSCLC.

Adenocarcinoma↗
PubMed2005

Evolving concepts in the pathology and computed tomography imaging of lung adenocarcinoma and bronchioloalveolar carcinoma.

PURPOSE: To review recent advances in pathology and computed tomography (CT) of lung adenocarcinoma and bronchioloalveolar carcinoma (BAC). METHODS: A pathology/CT review panel of pathologists and radiologists met during a November 2004 International Association for the Study of Lung Cancer/American Society of Clinical Oncology consensus workshop in New York. The purpose was to determine if existing data was sufficient to propose modification of criteria for adenocarcinoma and BAC as newly published in the 2004 WHO Classification of Lung Tumors, and to address the pathologic/radiologic concept of diffuse/multicentric BAC. RESULTS: Solitary small, peripheral BACs have an excellent prognosis. Most lung adenocarcinomas with a BAC pattern are not pure BAC, but rather adenocarcinoma, mixed subtype with invasive patterns. This applies to tumors presenting with a diffuse/multinodular as well as solitary nodule pattern. The percent of BAC versus invasive components in lung adenocarcinomas appears to be prognostically important. However, a consensus definition of "minimally invasive" BAC with a favorable prognosis could not be achieved. While recognition of a BAC component is possible, the diagnosis of BAC with exclusion of invasive adenocarcinoma cannot be made by small biopsy or cytology specimens. CONCLUSION: There is a need to work toward a mutual understanding and consensus between pathologists, clinicians, and researchers with the use of the term BAC versus adenocarcinoma. Future studies should make some attempt to quantitate these components and/or other features such as size of scar, size of invasive component, or pattern of invasion. Hopefully, this work will allow definition of a category of adenocarcinoma, mixed subtype with predominant BAC/minimal invasion and a favorable prognosis.

Adenocarcinoma↗
PubMed2005

Discordance between general and pulmonary pathologists in the diagnosis of interstitial lung disease.

BACKGROUND: Interstitial lung diseases (ILDs) often present diagnostic challenges to both the clinician and pathologist. Surgical lung biopsy (SLB) is often pursued in the evaluation of ILD and the clinician uses the histopathologic conclusions to guide management. However, the agreement between general and pulmonary pathologists in histopathologic diagnosis of ILD has not been established. OBJECTIVE: To determine the agreement between general and pulmonary pathologists in the histopathologic interpretation of ILDs and whether disagreements result in changes in clinical management. METHODS: We retrospectively reviewed all patients who underwent SLB for ILD at our institution, between 1996 and 2002. We compared the interpretations of general pathologists to those of pulmonary pathologists to evaluate the degree of inter-rater agreement. We assumed the specialist pathologist represented the "gold standard." We further determined if changes in the histopathologic diagnosis altered clinical management. RESULTS: Of 83 subjects who underwent SLB, 44 (mean age 58.5 +/- 14.2, 47.7% male) were examined by both general and specialty pathologists. There was poor agreement between the two sets of reviewers. The histopathologic interpretation by the specialist pathologist differed from the generalist in 52.3% of cases (kappa 0.21, P < 0.0001). This high rate of discordance led to frequent (60.0%) changes in clinical management. As a screening test for usual interstitial pneumonia, the observations of the general pathologist had moderate sensitivity and specificity (76.5% and 66.7%, respectively). CONCLUSIONS: General and pulmonary pathologists often differ in their interpretation of the histopathology in ILD. This significant discordance may have important clinical implications for patient care.

Adult↗
PubMed2005

Impact of chronic GVHD therapy on the development of squamous-cell cancers after hematopoietic stem-cell transplantation: an international case-control study.

Previous studies of recipients of hematopoietic stem-cell transplants suggest that graft-versus-host disease (GVHD) and its therapy may increase the risk for solid cancers, particularly squamous-cell carcinomas (SCCs) of the buccal cavity and skin. However, the importance and magnitude of these associations are not well characterized. We conducted a case-control study of 183 patients with posttransplantation solid cancers (58 SCCs, 125 non-SCCs) and 501 matched control patients within a cohort of 24,011 patients who underwent hematopoietic stem-cell transplantation (HSCT) at 215 centers worldwide. Our results showed that chronic GVHD and its therapy were strongly related to the risk for SCC, whereas no increase in risk was found for non-SCCs. Major risk factors for the development of SCC were long duration of chronic GVHD therapy (P < .001); use of azathioprine, particularly when combined with cyclosporine and steroids (P < .001); and severe chronic GVHD (P = .004). Given that most patients who received prolonged immunosuppressive therapy and those with severe chronic GVHD were also treated with azathioprine, the independent effects of these factors could not be evaluated. Additional analyses determined that prolonged immunosuppressive therapy and azathioprine use were also significant risk factors for SCC of the skin and of the oral mucosa. These data provide further encouragement for strategies to prevent chronic GVHD and for the development of more effective and less carcinogenic treatment regimens for patients with moderate or severe chronic GVHD. Our results also suggest that clinical screening for SCC is appropriate among patients exposed to persistent chronic GVHD, prolonged immunosuppressive therapy, or both.

Adolescent↗
PubMed2005

Physiology is a stronger predictor of survival than pathology in fibrotic interstitial pneumonia.

The histopathologic pattern provides the most important prognostic marker for idiopathic interstitial pneumonia; however, studies have suggested that short-term changes in lung function may be more important. We investigated the prognostic factors for fibrotic interstitial pneumonia. The clinical features and follow-up course of 179 patients (131 with idiopathic pulmonary fibrosis and 48 with nonspecific interstitial pneumonia; 41 fibrotic types and 7 cellular) were analyzed retrospectively. The lung function indices improved or stabilized in most patients with fibrotic nonspecific interstitial pneumonia in contrast to the deterioration or stable condition of most patients with idiopathic pulmonary fibrosis. The 5-year survival of patients with fibrotic nonspecific interstitial pneumonia (76.2%) was better than for those with idiopathic pulmonary fibrosis (43.8%) (p = 0.007). Multivariate analysis at the time of presentation revealed that pathologic pattern, age, and diffusion capacity had important prognostic implications. However, after 6 months of follow-up, changes in FVC, initial diffusion capacity, and sex were the only independent prognostic factors, with no additional prognostic information conferred by the histologic diagnosis. Our data confirmed the importance of physiological parameters including short-term change in FVC. However, at the time of diagnosis, histopathology was important for the prediction of prognosis and future change in lung function.

Biopsy↗
PubMed2005

Prognostic implications of molecular and immunohistochemical profiles of the Rb and p53 cell cycle regulatory pathways in primary non-small cell lung carcinoma.

PURPOSE: Many studies have highlighted the aberrant expression and prognostic significance of individual proteins in either the Rb (particularly cyclin D1, p16INK4A, and pRb) or the p53 (p53 and p21Waf1) pathways in non-small cell lung cancer. We hypothesize that cumulative abnormalities within each and between these pathways would have significant prognostic potential regarding survival. EXPERIMENTAL DESIGN: Our study population consisted of 106 consecutive surgically resected cases of predominantly early-stage non-small cell lung cancer from the National Cancer Institute-Mayo Clinic series, and assessment of proteins involved both immunohistochemical (cyclin D1, p21Waf1, pRb, p16INK4A, and p53) and mutational analysis (p53) in relationship to staging and survival. RESULTS: Cyclin D1 overexpression was noted in 48% of the tumors, p16INK4A negative in 53%, pRb negative in 17%, p53 immunopositive in 50%, p53 mutation frequency in 48%, and p21(Waf1) overexpression in 47%, none with prognostic significance. Cyclin D1 overexpression in pRb-negative tumors revealed a significantly worse prognosis with a mean survival of 2.3 years (P = 0.004). A simultaneous p53 mutation dramatically reduced the mean survival time to 0.9 years (P = 0.007). Cyclin D1 overexpression with either a p53 mutation or a p53 overexpression was also associated with a significantly poorer prognosis (P = 0.0033 and 0.0063, respectively). CONCLUSIONS: Some cumulative abnormalities in the Rb and p53 pathways (e.g., cyclin D1 overexpression and p53 mutations) significantly cooperate to predict a poor prognosis; however, the complexity of the cell cycle protein interaction in any given tumor warrants caution in interpreting survival results when specific protein abnormalities are taken in isolation.

Aged↗