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Chen-Tu Wu

Publications and source records attributed to Chen-Tu Wu.

15 recordsLinked to original sources

Clonality and prognostic implications of p53 and epidermal growth factor receptor somatic aberrations in multiple primary lung cancers.

PURPOSE: For treatment decision and prognostic applications, we evaluated p53/epidermal growth factor receptor (EGFR) somatic aberrations in multiple primary lung cancers to differentiate multifocal tumors from intrapulmonary metastasis. EXPERIMENTAL DESIGN: Fifty-eight multiple primary lung cancers of 1,037 patients in a 10-year period were identified to investigate somatic mutations and altered expression of p53 and EGFR for clonality assessment. Genomic DNA was extracted from microdissected cells of paraffin-embedded multiple primary lung cancer tissues. Overexpression and somatic mutations in exons of p53 (exons 5-8) and tyrosine kinase domain of EGFR (exons 18-22) were examined by immunohistochemical staining and DNA sequencing, respectively. RESULTS: High frequency of somatic mutations in p53 (33 of 58, 56.9%) and/or EGFR (44 of 58, 75.9%) resulted in high discrimination rate of tumor clonality (50 of 58, 86.2%) of multiple primary lung cancers. Twenty-two cases (37.9%) were assessed as having the same clonality and 28 cases (48.3%) were determined as having different clonality, which further supported the carcinogenic theory of field cancerization. Notably, the occurrence of lymph node metastasis was more commonly observed in tumors with the same clonality (P = 0.045) and was associated with poor patient 5-year survival rate (P = 0.001). However, no correlation was found between tumor clonality and patient survival (P = 0.630). The EGFR somatic aberrations in 58 multiple primary lung cancers, including vascular invasion associated with EGFR overexpression (P = 0.012) and mutation (P = 0.025), further suggested the potential benefits of target therapy of inoperable multiple primary lung cancers. CONCLUSIONS: Our results suggest that analysis of somatic alterations in p53 and EGFR can significantly improve the clonality assessment and impact management of multiple primary lung cancer patients.

DNA Mutational Analysis↗

Expression of the estrogen receptor beta in 37 surgically treated pulmonary sclerosing hemangiomas in comparison with non-small cell lung carcinomas.

Sclerosing hemangioma (SH) of the lung is an uncommon tumor with a predilection for middle-aged women. This special phenomenon prompted us to examine SH for the expression of ERalpha (human estrogen receptor) and ERbeta (a second isoform of estrogen receptor). To investigate the staining pattern of these tumors, we also stained lung tissues from patients with non-small cell lung carcinomas and nonneoplastic type II pneumocytes for comparison. Thirty-seven pulmonary SHs and 301 non-small cell lung cancers specimens were explored. Expression of ERalpha and ERbeta was immunohistochemically measured. The overall frequency of overexpression for ERbeta was 91.9%. It was detected in both female (in 91.4% of 35 cases) and male (in 100.0% of 2 tumors from men) patients. There was ERbeta overexpression in all 9 tumors of solid pattern, 6 of 7 tumors of papillary pattern, all 4 tumors of sclerotic pattern, 12 of 13 tumors of hemorrhagic pattern, and 3 of 4 tumors of mixed pattern. The staining pattern of the neoplastic cells of the SH was similar to that of type II pneumocytes adjacent to the tumor rather than that of non-small cell lung cancers, in which the frequency of ERbeta overexpression was 45.8%. However, there was no ERalpha detectable in these neoplasms. Estrogen receptor beta overexpression is very frequent in pulmonary SHs, which is similar to that of alveolar cells but quite different from non-small cell carcinoma.

Adult↗

Surgical lung biopsy for diffuse pulmonary disease: experience of 196 patients.

OBJECTIVE: Surgical lung biopsy is considered the final method of diagnostic modality in patients with undiagnosed diffuse pulmonary disease. Nevertheless, the effect of surgical lung biopsy on the diagnosis, treatment, and outcome of the patient still remains controversial. This study reviewed the experiences of surgical lung biopsies in 196 consecutive patients during the past 7 years. METHODS: Surgical lung biopsy was performed after achievement of general anesthesia through video-assisted thoracoscopic surgery or a 7-cm minithoracotomy. Biopsy specimens were swabbed for aerobic and anaerobic bacterial, fungal, and mycobacterial cultures. The sections of specimens were routinely stained with hematoxylin and eosin, and acid-fast, Gomori methenamine silver, Gram stain, or other special stains were added if necessary. RESULTS: The pathologic diagnosis after surgical lung biopsy included infection (30.6%), interstitial pneumonia or fibrosis (21.9%), diffuse alveolar damage (17.3%), neoplasm (13.3%), autoimmune diseases (8.2%), and others (8.2%). After surgical lung biopsy, 165 (84.2%) patients had changes in their therapy, 124 (63.3%) patients had clinical improvement of their conditions, and 119 (60.7%) patients survived to hospital discharge. Comparison between immunocompromised and immunocompetent patients showed that diagnosis of infection was significantly higher ( P < .01) in the former group (41.2% vs 20.2%). In addition, there was no significant difference in the distribution of diagnosis and rate of change in therapy between the respiratory failure and nonrespiratory failure groups. However, the rates of response to therapy and patient survival were significantly lower in the respiratory failure group (51.2% and 41.5%) than in the nonrespiratory failure group (71.9% and 78.1%, P < .05). There was no surgical mortality directly related to the procedure. The surgical morbidity rate was 6.6%. CONCLUSION: Surgical lung biopsy is a safe and accurate diagnostic tool for diffuse pulmonary disease. For a large proportion of the patients, change of therapy and then clinical improvement can be achieved after surgical lung biopsy. Surgical lung biopsy should be considered earlier in patients with undiagnosed diffuse pulmonary disease, especially when the respiratory condition is deteriorating.

Adolescent↗

The significance of estrogen receptor beta in 301 surgically treated non-small cell lung cancers.

OBJECTIVE: Estrogen receptor expression in lung cancer has been understudied, particularly in light of its potential biologic importance in the epidemic of lung cancer in women. The expression of estrogen receptors was investigated to better understand the possible role of sex hormones in lung cancer. METHODS: A total of 301 patients with surgically resected non-small cell lung cancers of stages I to III were explored. Sections of paraffin-embedded tumor samples were stained with estrogen receptor alpha and estrogen receptor beta antibodies. Tumors with moderate-to-strong nuclear staining in at least 50% of the tumor cells were scored as positive for overexpression. RESULTS: The overall frequency of overexpression for estrogen receptor beta was 45.8% (138/301). It was detected most frequently in female patients (in 54.3% of 127 tumors vs 39.7% of 174 tumors in men, P = .012). However, there was no estrogen receptor alpha nuclear staining detectable in non-small cell lung cancers. Interestingly, a significant correlation between estrogen receptor beta expression, stage of disease, grade of differentiation, smoking status, vascular invasion, and survival in patients with stage II and III disease was found. By using multivariate analysis of survival among patients with stage II and III disease, estrogen receptor beta overexpression, stage II tumor, well differentiation, nonsmoking status, and lack of vascular invasion were significantly favorable prognostic factors. CONCLUSIONS: The results presented here show for the first time that immunohistochemical expression of estrogen receptor beta can be used as a prognostic indicator in patients with surgically resected stage II and III non-small cell lung cancers. These observations might offer a possibility for hormonal therapy in patients with lung cancer.

Adult↗

Primary orbital leiomyosarcoma.

An 84-year-old woman presented with a right upper eyelid nodule, first noted 1 month earlier. Incisional biopsy revealed leiomyosarcoma, which was subsequently treated with wide excision and adjunctive radiotherapy. There has been no evidence of tumor recurrence in 3 years of follow-up.

Aged, 80 and over↗

Loosening of total hip arthroplasty with a prosthesis employing a skirted femoral head.

In total hip arthroplasty, a modular femoral head with a flange increases the head-neck strength and compensates the leg length, but results in a decreased head-to-neck diameter ratio. Studies have shown increased chance of impingement and incidence of dislocation associated with a skirted femoral head component. However, the relation between implant loosening and the skirted neck has not been well demonstrated. We report a 41-year-old male patient with aseptic loosening of total hip arthroplasty due to osteolysis of both acetabular and femoral components 5 years after surgery. The retrieved prostheses demonstrated polyethylene wear due to impingement of the skirted head during hip flexion. Pathologic examination showed prominent foreign body reaction. Prosthetic impingement occurs due to malposition of components and extreme posture. A decreased head-to-neck diameter ratio further compromises prosthetic range of motion. A skirted femoral head component should be used with caution.

Adult↗

The utility and limitation of thyroid transcription factor-1 protein in primary and metastatic pulmonary neoplasms.

Thyroid transcription factor-1 (TTF-1) is a tissue-specific transcription factor expressed in the thyroid and lung. The clinical utility and limitation of TTF-1 in primary or metastatic carcinomas of the lung have not been previously studied in detail. We examined TTF-1 expression in 510 primary lung and 107 metastatic neoplasms. TTF-1 was detectable in 4/99 (4%) squamous cell carcinomas, 169/176 (96%) solitary adenocarcinomas, 34/34 (100%) multifocal adenocarcinomas, 1/1 (100%) signet ring cell carcinoma, 16/20 (80%) mucinous adenocarcinomas, 23/23 (100%) nonmucinous bronchioloalveolar carcinomas, 19/36 (53%) small cell carcinomas, and 39/44 (89%) sclerosing hemangioma. TTF-1 was absent in all eight carcinoids, three atypical carcinoids, 23 pleomorphic carcinomas, 25 lymphoepithelioma-like carcinomas, the sarcomatous component of one pseudomesotheliomatous carcinoma, and one mesothelioma. In four combined small cell carcinomas and 12 adenosquamous carcinomas, TTF-1 expression was only demonstrated in the adenocarcinoma component. There were 78 TTF-1 non-immunoreactive metastatic cases from 22 livers, 20 colorectums, 10 breasts, six nasopharynx, four larynx, four ovaries, three salivary glands, three esophagus, two adrenal glands, two kidneys, one bile duct, and one endometrium. TTF-1 was also detected in all 10 cervical lymph nodes, seven brain, and 6/7 (86%) bony tissues of 24 patients with metastatic carcinomas of unknown primary site, but it was absent in 125 patients with metastatic carcinomas other than lung origin in cervical lymph nodes, brain, and bony tissues. These results indicate the clinical usefulness and limitation in certain primary and metastatic lung neoplasms.

Adenocarcinoma↗

Mycotic Aneurysm Caused by Streptococcus constellatus subsp. constellatus.

An infected mycotic aneurysm due to Streptococcus constellatus subsp. constellatus has not previously been reported. We report on this condition in an 87-year-old woman who had aggravating abdominal pain and a large fusiform aneurysm over the thoracic-abdominal aorta with mural thrombus. Isolates from two sets of blood cultures and the debrided tissue were identified as S. constellatus subsp. constellatus by their biochemical reaction profiles, compatible 16S rRNA gene sequencing results, and sequencing results for the partial groESL gene and the 16S-23S intergenic spacer region.

Aged↗

Angiomyofibroblastoma of the vulva.

Angiomyofibroblastoma is a rare, recently described, distinctive benign mesenchymal tumor that occurs mainly in the vulvar region of premenopausal women. We report a case of angiomyofibroblastoma of the vulva. A 45-year-old woman reported a small, painless nodule on the left vulva which rapidly enlarged during the 6 months before she visited the hospital. Local examination showed a pedunculated, mobile mass on the superior aspect of the left labium majus (13 x 12 x 10 cm) with elastic texture. Left vulvectomy was performed and the excised specimen revealed a well-defined and multilobulated tumor with edematous changes on gross examination. Microscopically, the tumor had alternate hyper- and hypocellular areas characterized by benign-looking round- to spindle-shaped cells with eosinophilic cytoplasm. The tumor cells were admixed with scattered thin-walled vessels in an edematous stroma. Immunohistochemical analysis was diffusely positive for desmin, estrogen receptor and progesterone receptor; reactive in small focus for actin; and negative for S-100 and CD34. Angiomyofibroblastoma, a mesenchymal tumor, was diagnosed. The postoperative course was smooth with no recurrence during the following 8 months. Simple excision for angiomyofibroblastoma is recommended because local recurrence or metastasis has not been reported.

Angiofibroma↗

Specific induction of the high-molecular-weight microtubule-associated protein 2 (hmw-MAP2) by betel quid extract in cultured oral keratinocytes: clinical implications in betel quid-associated oral squamous cell carcinoma (OSCC).

Betel quid (BQ) chewing, a popular habit in numerous Asian countries including India and Taiwan, has a strong correlation with an increased risk of oral squamous cell carcinoma (OSCC). While substantial efforts have been made to test the cytotoxic, genotoxic and mutagenic effects of BQ extract and its components, the disease mechanisms underlying BQ-induced oral carcinogenesis remain obscure. Here, we show that a neuronal protein, microtubule-associated protein 2 (MAP2), was induced by BQ extract in cultured normal human oral keratinocytes (NHOKs). Subsequent analyses demonstrated that such induction was more eminent and consistent in the high-molecular-weight isoform of MAP2 (hmw-MAP2) than that in its low-molecular-weight counterpart (lmw-MAP2). Furthermore, we analyzed expression of hmw-MAP2 protein in 88 oral specimens consisting of clinicopathologically pre-malignant (leukoplakia) and malignant (OSCC) lesions, along with their adjacent normal mucosa. Immunohistochemistry revealed that, with the exposure to BQ, the hmw-MAP2 was over-expressed in 41.2% (7/17) of OSCC, 11.2% (1/9) of leukoplakia and none (0/19) of normal mucosa. In contrast, expression of the hmw-MAP2 was barely detected in BQ-free OSCC. These results suggest a significant correlation between expression of the hmw-MAP2 and BQ-associated progression of oral carcinogenesis (P=0.0046). Interestingly, the hmw-MAP2 was found to preferentially express in histopathologically less differentiated OSCC (P=0.014); the percentages of positive staining in poorly, moderately and well differentiated OSCC were 62.5, 21.4 and 7.1%, respectively. However, BQ chewing appeared to have marginal correlation with such propensity. Finally, we show that the majority of hmw-MAP2-positive poorly differentiated lesions were also histopathologically invasive. Taken together, these findings suggest the possibility that the hmw-MAP2 may be a diagnostic marker for BQ-chewing lesions and a potential therapeutic target. To our knowledge, this study has provided the first clinical implication that closely links a cytoskeletal protein to BQ-associated oral cancer.

Areca↗

Unstratified chemotherapy for non-metastatic osteosarcoma of the extremities in children.

BACKGROUND AND PURPOSE: The superiority of changing postoperative chemotherapy of osteosarcoma based on histological response of the primary tumor over non-tailored chemotherapy has not been confirmed. This multicenter study evaluated the effectiveness of an intensive unstratified chemotherapy regimen in Taiwanese children with osteosarcoma. METHODS: Fifty patients younger than 18 years of age with previously untreated non-metastatic osteosarcoma of the extremities were enrolled. Patients were treated with pre- and postoperative chemotherapy, and surgery. Definitive surgery was scheduled in week 7 and postoperative chemotherapy was uniform without stratification regardless of histologic response. RESULTS: Chemotherapy toxicities were considerable, but manageable. Treatment delay and decreased dose-intensity were common. There was one treatment-related mortality. Forty three patients (86%) received limb salvage surgery and 14 patients (33%) had a good histologic response to preoperative chemotherapy. With a median follow-up of 47.1 months, the 7-year event-free and overall survival rates were 51.6% and 67.6%, respectively. CONCLUSIONS: This was the first multicenter study on the treatment of osteosarcoma from Taiwan. The results suggest that a non-tailored regimen may serve as an alternative treatment strategy in the management of osteosarcoma, particularly when histologic assessment of the tumor response is not available.

Adolescent↗

Concomitant intramyocardial and epicardial vasculitis in an autopsied heart allograft for cardiac rhabdomyosarcoma.

Primary cardiac tumours are rare, with only one quarter of the patients being malignant. The vast majority of malignant neoplasms of the heart are sarcomas. We describe a patient of primary cardiac rhabdomyosarcoma presented as coronary artery disease and recurrent myocardial infarction. Histopathologic finding of the excised native heart revealed a high grade pleomorphic rhabdomyosarcoma in the myoepicardial portion of the anterior wall with rupture. The accompanying unusual feature was myocardial infarction because of tumour emboli of the left anterior descending and left circumflex coronary arteries. After transplantation, the patient developed mild to moderate acute cellular rejection of the transplanted heart on post-transplantation day 1, 8, and 44, respectively. Unfortunately, he expired on the post-transplantation day 47 because of acute rejection, presenting as concomitant intramyocardial and epicardial lymphocytic vasculitis and multifocal myocardial ischaemia. We found that this uncommon medial lymphocytic vasculitis lesion was mediated by T cells and also by antibody directly against smooth muscle cells of small arteries. The consequence of such immune response would be compromised myocardial oxygenation resulting in allograft failure.

Adult↗

The significance of E-cadherin and alpha-, beta-, and gamma-catenin expression in surgically treated non-small cell lung cancers of 3 cm or less in size.

OBJECTIVES: Expression of the cell-cell adhesion molecules E-cadherin and alpha-, beta-, and gamma-catenin seems closely related to tumor invasiveness. The relationship between the expression and clinicopathologic characteristics in surgically resected non-small cell lung cancers of 3 cm or less in size was studied. The relationship to patient survival was analyzed. METHODS: A total of 115 patients with surgically resected lung cancers of 3 cm or less in size were enrolled in this study. Expression of E-cadherin and alpha-, beta-, and gamma-catenin was immunohistochemically measured. The chi(2) test was used to correlate this expression with clinicopathologic parameters. Their influence on patient survival was evaluated with the Cox proportional hazards model. RESULTS: There was a positive correlation between E-cadherin and catenin expression in lung cancers. In general, E-cadherin and catenin expression were greater in tumors that were either bronchioloalveolar carcinomas or adenocarcinomas, well differentiated, early stage, peripheral, and without vascular or pleural invasion. By using multicovariate analysis of patient survival, only early-stage and peripheral tumors were significantly favorable prognostic factors. Further analysis of the group of patients with early-stage disease showed that higher alpha-, beta-, or gamma-catenin expression was a favorable prognostic indicator. CONCLUSION: Expression of alpha-, beta-, or gamma-catenin can be used as a prognostic indicator in patients with surgically resected stage I non-small cell lung cancers of 3 cm or less in size.

Adenocarcinoma↗

New aspects in clinicopathologic and oncogene studies of 23 pulmonary lymphoepithelioma-like carcinomas.

Lymphoepithelioma-like carcinoma, an uncommon epithelial tumor, has been described as being closely associated with Epstein-Barr virus (EBV) infection in many organs, especially the nasopharynx. We experienced 23 cases of lymphoepithelioma-like carcinoma arising in the lung from 2498 lung cancer patients in the Cancer Registry of our hospital. Seven patients were male and 16 were female. All patients were Chinese. Their ages ranged from 42 to 80 years. Six patients were smokers and 17 were nonsmokers. The tumor sizes ranged from 1.2 to 11.0 cm. All tumors showed the typical syncytial growth pattern of undifferentiated epithelial cells with a significant CD8+ T-lymphocyte reaction. EBV serology revealed prior infection in all 15 serum-available patients, all of whom were also found by in situ hybridization to have the virus genome. In addition, the higher the EBV serology titer, the larger the tumor size and the higher the staging would be. EBV viral capsid antigen IgG level remained elevated despite response to therapy. Nearly all cases had bcl-2 oncoprotein expression, but the detection rate of latent membrane protein-1, p53, and c-erb B-2 expression was extremely low. The encouraging chemotherapy response for advanced stage disease is also discussed.

Adult↗