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Dongfeng Tan

Publications and source records attributed to Dongfeng Tan.

At least 37 records · Page 2Linked to original sources
PubMed2005

Frequent trefoil factor 3 (TFF3) overexpression and promoter hypomethylation in mouse and human hepatocellular carcinomas.

Expression profiling analysis revealed ectopic high expression of mouse TFF3 in non-tumor liver tissues from the hepatocellular carcinoma (HCC) susceptible PWK/Rbrc strain. TFF3 is a member of the trefoil factor family peptides, which are small secreted proteins regulating mucosal regeneration and repair, and which are overexpressed during inflammatory processes and cancer progression. We, therefore, analyzed the TFF3 expression extensively in mouse and human HCCs. Expression of the mouse TFF3 gene was significantly increased in 6 out of 7 HCCs from a PWK spontaneous tumor model and in all 7 HCCs from an SV40T antigen-induced transgenic MT-D2C57BL/6 model. In humans, 8 of 20 HCCs (40%) had overexpression of TFF3 in both mRNA level and protein level. We then analyzed DNA methylation patterns of the TFF3 promoter region to evaluate expression regulation of promoter methylation. In mouse HCCs, we demonstrated that two CpGs, at positions -992 and +109, were hypomethylated in 13 of 14 mouse HCCs. In human HCCs, hypomethylation at CpG -260 was associated with TFF3 overexpression (p=0.04). These results indicate that TFF3 overexpression may be a critical process in mouse and human hepatocellular carcinogenesis, and the specific promoter CpG hypomethylation may be one of the regulation mechanisms of TFF3 overexpression in HCCs.

Animals↗
PubMed2004

Upregulation of the tissue inhibitor of metalloproteinase-1 protein is associated with progression of human non-small-cell lung cancer.

PURPOSE: Tissue inhibitors of metalloproteinases (TIMPs) are naturally occurring inhibitors of matrix metalloproteinases (MMPs). It has been shown that TIMP-1 may be a multifunctional protein. Little is known about the role of TIMP-1 in progression and metastasis of human lung cancer (tumor inhibiting or tumor promoting), although studies using a variety of techniques have analyzed the expression of TIMP-1 mRNA and/or protein in human cancers. PATIENTS AND METHODS: We examined the expression of TIMP-1 protein by immunohistochemistry in patients (n = 160) with primary respectable (stage I to IIIA) non-small-cell lung cancer (NSCLC). RESULTS: Twenty-seven percent of the tumors (43 of 160) demonstrated elevated expression of this protein. We demonstrate that overexpression of TIMP-1 protein is associated with an adverse outcome. In addition, disease stage, patient's age, and performance status were all significantly related to survival. In multivariate analyses, patients with high TIMP-1 expression had a 90% increased risk of death when compared with those with low expression (relative risk, 1.92; 95% CI, 1.19 to 3.09; P =.008). TIMP-1 expression did not correlate with expression of MMP-2 and MMP-9. CONCLUSION: These results suggest that TIMP-1, independent of its inhibiting activity of MMPs, may have other function(s) critical for NSCLCs. The significance of our results is two-fold. The adverse outcome in patients with overexpression of TIMP-1 indicates its potential prognostic value in NSCLC. Thus, TIMP-1 overexpression may serve to help identify patients with particularly aggressive disease for adjuvant treatments. In addition, the TIMP-1 molecule may represent a novel therapeutic target for treatment of some NSCLCs.

Adult↗
PubMed2004

Intestinal tumor progression is associated with altered function of KLF5.

Krüppel-like transcription factors have been linked to cell growth regulation and tumorigenesis in a number of systems. In the intestinal epithelium, expression of KLF5 (IKLF/BTEB2) is limited to proliferating crypt cells, indicating a growth-promoting role. Consistent with this role, we demonstrate that expression of KLF5 in non-transformed intestinal epithelial cells (ileal IEC-18 and Immorto-Min Colon Epithelial (IMCE) cells) enhances colony formation, cyclin D1 transcription, and cell growth. However, in contrast to these effects in non-transformed cells, KLF5 reduced colony number, failed to enhance cyclin D1 transcription, and was negatively correlated with cell growth in colon cancer cell lines. The relationship between tumor progression and KLF5 was further investigated using Ras-mediated transformation of IEC-18 and IMCE cells as syngeneic models. Ras-transformation recapitulated differences in the effects of KLF5 on cell growth and cyclin D1 transcription, providing a direct link between intestinal tumor progression and altered function of KLF5. Ras-transformation also markedly down-regulated KLF5; further analysis indicated that reduced expression of KLF5 mRNA and destabilization of KLF5 protein occur in intestinal tumors. Reduced levels of KLF5 mRNA were also detected in APC(min) mouse and human familial adenomatous polyposis adenomas compared with normal crypt epithelium, indicating that down-regulation of KLF5 is an early event in intestinal tumorigenesis in vivo. Collectively, these data indicate that intestinal tumor progression is associated with a change in the growth-related functions of KLF5 and that intestinal tumors down-regulate KLF5 expression by multiple mechanisms.

Adenoma↗
PubMed2004

Lipomatous hemangiopericytoma of the head and neck: immunohistochemical and DNA ploidy analyses.

BACKGROUND: Lipomatous hemangiopericytoma (LHPC) is a newly described rare soft tissue tumor with unpredictable biologic behavior and is difficult to diagnose by conventional histologic parameters. The molecular analyses of this entity to date are sparse. Only a few cases of LHPC have been reported. Although one case of LHPC in the sinonasal region was briefly reported, this is the first case in the head and neck region with detailed clinicopathologic features and molecular analysis of this entity. METHODS: We reported a case of LHPC in a 55-year-old woman with a slowly growing lesion in the occipital area that was diagnosed by CT and MRI and removed surgically. Immunohistochemical and DNA ploidy analyses were performed. RESULTS: A panel of 16 markers was included for immunohistochemical analysis. Diffuse immunopositivity of CD57 in our case provides supportive evidence that LHPC is linked with HPC because this marker is also present in approximately 50% of conventional HPCs. CD57 should be used in the immunohistochemical panel in any lesion suspected to be LHPC. Furthermore, CD57 along with CD34 and XIIIa is thought to stain for primitive mesenchymal stem cells, suggesting a bimodal/multimodal differentiation of LHPC. By flow cytometry, we found that tumor cells were 100% diploid with the S-phase fraction (SPF) being 3.21%. A significant positive correlation was detected between nuclear proliferating index and SPF (p < 0.001, by Spearman analysis). These findings provide molecular evidence indicating a benign nature of LHPC. CONCLUSIONS: Contrary to the old belief that HPC has an aggressive nature, this variant of tumor looks less aggressive. The patient was followed for 1 year without any evidence of recurrence, supporting our pathologic hypothesis.

Biomarkers, Tumor↗
PubMed2004

Prognostic significance of gelsolin expression level and variability in non-small cell lung cancer.

BACKGROUND: Gelsolin is an actin-binding protein that mediates cellular motility and maintains the integrity of cytoskeletal structure. Diminished expression of gelsolin has been observed in human cancer cell lines and tumors. Studies of the prognostic effect of gelsolin expression (GE) in non-small cell lung cancer (NSCLC) are rare and results are inconsistent to date. The present study used immunohistochemistry to evaluate the prognostic effect of gelsolin expression in 155 patients with resectable NSCLC. METHODS: Detection of gelsolin in tumor cells was performed by immunohistochemistry, and two approaches to classification were used to describe expression: expression level (negative, reduced or high) and expression uniformity (uniform or variable). Expression level was determined by a weighted index of intensity of staining (i.e., overall tendency) in the specimen. Expression uniformity was based on the presence or absence of variability in immunostaining within the tumor section. Chi-square test, student t-test, Cox proportional hazards regression and Kaplan-Meier survival analysis were used in data analyses. RESULTS: After controlling for covariates, high level gelsolin expression was significantly associated with poor survival compared with negative gelsolin expression in NSCLC, and this adverse prognostic effect was specific to patients with stage II tumors and for patients with squamous cell carcinomas. Similarly, variable gelsolin expression was significantly associated with poor survival compared with uniform gelsolin expression and this adverse prognostic effect was also specific to patients with stage II tumors and for patients with squamous cell carcinomas. CONCLUSION: High level gelsolin expression and variable gelsolin expression are adverse prognostic factors for NSCLC in this study, which might manifest the high motility and heterogeneity of tumor cells, two distinguishing characteristics for tumors with potentially enhanced invasive and dissemination capabilities.

Aged↗
PubMed2004

Altered E-cadherin and epidermal growth factor receptor expressions are associated with patient survival in lung cancer: a study utilizing high-density tissue microarray and immunohistochemistry.

E-cadherin (E-cad) and epidermal growth factor receptor (EGFR) are important cell adhesion and signaling pathway mediators. This study aimed to assess their expression in lung adenocarcinoma (AdC) and squamous cell carcinoma (SCC) and their association with clinicopathologic variables. In all, 130 resectable lung cancers (stages I-IIIA) were studied using a high-density tissue microarray. Two to three cores from each case were arrayed into three blocks using a Beecher system. Immunohistochemistry was performed using an avidin-biotin complex method and monoclonal antibodies against E-cad and EGFR. Unequivocal membrane staining in >10% of tumor cells was considered as a positive expression of E-cad and EGFR. Markers expression and coexpression were analyzed against clinicopathologic variables (age, gender, smoking status, performance status, weight loss, histology, grade, stage, and lymph node involvement) and patient survival. There were 118, 126, and 115 cases that were fully assessable for E-cad, EGFR, and both markers, respectively. For E-cad, 65 cases (55%) were positive (+), 53 (45%) were negative (-); 23 cases of the negative group had only cytoplasmic staining. For EGRF, 43 cases (34%) were (+), and 83 (66%) were (-). There was no significant association between E-cad or EGFR, and any of the clinicopathologic variables except for an association between EGFR(+) and SCC histologic type. Both negative and cytoplasmic staining of E-cad correlated with shorter patient survival with P=0.008 and 0.002, respectively. EGFR expression did not correlate with patient survival; however, patients with E-cad(-)/EGFR(+) phenotype had poorer survival than those with E-cad(+)/EGFR(-) (P=0.026). Our study suggests that lung AdC and SCC may be stratified based on expression of E-cad and EGFR with the E-cad(-)/EGFR(+) expression having a worse disease outcome. Moreover, the cytoplasmic expression of E-cad may represent an altered localization of this protein in association with tumorigenicity.

Adenocarcinoma↗
PubMed2004

Definition of a region of loss of heterozygosity at chromosome 11q23.3-25 in head and neck squamous cell carcinoma using laser capture microdissection technique.

To date, loss of heterozygosity (LOH) studies on HNSCC have had limited success in identifying a confined region of loss on chromosome 11q partially due to the heterogeneous nature of tumor tissue examined. Additionally, little is known about the role of the 11q allelic deletion in HNSCC tumorigenesis and current reports are conflicting. The aim of this study was to better define LOH at distal 11q by using combination of a pure cell population procured by laser capture microdissection (LCM) and subsequent sensitive PCR amplification of polymorphic microsatellites. This study analyzed HNSCC for LOH using a panel of 5 microsatellite markers spanning 11q23-25. Thirty-four paired DNA samples from tumor and autologous normal tissue were harvested by LCM technique to ensure a pure cell population for PCR amplification. Approximately 2000 to 3000 cells were procured from each sample. Twenty-one of 34 cases (62%, P < 0.001) showed LOH on at least one of the loci examined. The highest frequency of LOH was found at the 11q23.3-25 segment, with 44% at marker D11S968 and 35% at marker D11S1316. A distinct novel region of frequent LOH at 11q23.3-25, defined by D11S1316 and D11S968, was identified. No allelic loss was found in any normal squamous tissue samples. To study LOH in HNSCC, combination of pure cell population procurement by LCM and sensitive PCR provides a more accurate approach than the conventional method using a bulk of heterogeneous tissue. A novel region of LOH at 11q23.3-25 was defined. LOH in this region may harbor putative tumor suppressor gene(s) critical for HNSCC. Furthermore, these allelic losses were not found in any non-neoplastic squamous tissue samples, clarifying prior discrepant data.

Adult↗
PubMed2004

Multimodality therapy for thymic carcinoma (TCA): results of a 30-year single-institution experience.

SUMMARY: The aim of this study was to correlate the clinicopathologic features and therapeutic approaches with the outcome of patients with thymic carcinoma (TCA), an aggressive, uncommon malignancy of the anterior mediastinum. TCA is morphologically distinct from thymoma, a cytologically bland, often encapsulated, locally invasive, rarely metastatic tumor. The Roswell Park Cancer Institute tumor registry was used to identify patients with TCA or invasive thymic neoplasm of the epithelial type (TNET). Between 1971 and 2001, 22 patients had a pathologic diagnosis of TCA and/or TNET. The mean age at diagnosis was 53 years (range: 19-77), and the male/female ratio was 3:1 (16/6). Initial symptoms were respiratory in about half the patients (10/22). Complete surgical resection was done in five patients. Postoperative cisplatin-based chemotherapy and radiation was administered to seven patients. Pathologic examination showed low grade(n = 14), intermediate grade (n = 7), and high grade (n = 1) TCA. Capsular invasion was present in 83% of the specimens. As of June 2002, nine patients are alive and eight are disease free. The median survival is 44.7 months. Locally invasive disease precluded complete surgical resection in more than half of our cases. Incomplete surgical resection did not preclude long-term survival if multimodality platinum-based therapy was used.

Adult↗
PubMed2004

Overexpression of urinary plasminogen activator (uPA) protein and mRNA in thyroid carcinogenesis.

OBJECTIVE: Urinary plasminogen activator (uPA), a protease, is one of the critical components of tumor invasion and metastasis. Its expression in thyroid carcinoma and potential role in thyroid tumorigenesis are unknown. The objective of this study was to determine whether uPA is differentially expressed in benign and malignant thyroid tumors. DESIGN: uPA expression was evaluated by immunohistochemistry (IHC) in 20 thyroid tumors (six classic papillary thyroid cancers (PTC) and three tall cell variants (TCV) and 11 adenomas). To validate IHC results, in situ hybridization was performed on both adenomas and cancer tissues to explore the expression of uPA at the mRNA level. The Fisher exact test was used to compare protein as well as mRNA expressions in adenomas and thyroid cancer. RESULTS: Intense granular cytoplasmic staining for uPA was observed in five of nine (56%) of thyroid cancers: 2/6 classic PTC (33%) and all tall cell variant PTC. Furthermore, uPA mRNA expression was found in the malignant thyroid epithelium but not in adjacent normal thyroid follicles or the stromal elements. None of the adenomas expressed uPA (P = .008). uPA staining was absent in histologically normal follicles adjacent to malignant thyroid follicles. CONCLUSIONS: uPA is expressed in thyroid carcinoma but not in benign adenomas or normal adjacent follicles. The selective expression of uPA in thyroid carcinoma provides evidence that uPA is useful in distinguishing benign and malignant thyroid neoplasms. More importantly, uPA may represent molecular target for therapeutic treatment of this malignancy.

Adenocarcinoma, Papillary↗
PubMed2004

Parathyroid carcinoma: a multicenter review of clinicopathologic features and treatment outcomes.

We conducted a retrospective study of 13 patients with parathyroid carcinoma to assess their clinical characteristics and surgical outcomes. Study parameters included patient demographics, survival, treatment response, and recurrence. We found that all patients who had undergone local tumor excision developed a recurrence, compared with only 33% of those available for follow-up after en bloc tumor resection. Based on these findings, we recommend en bloc tumor resection as the initial treatment of choice for patients diagnosed with parathyroid carcinoma.

Adult↗
PubMed2004

Development of head and neck squamous cell carcinoma is associated with altered cytokine responsiveness.

Growth of head and neck squamous cell carcinoma (HNSCC) is generally associated with an inflammatory component. It is hypothesized that these tumor cells develop mechanisms to evade the growth inhibitory effects of cytokines that are present in the tumor microenvironment. This study determined the changes in responsiveness to inflammatory cytokines that accompany the transition of normal to transformed epithelial cells. Paired primary cultures of normal epithelial cells (NEC) and SCC cells were established from 16 patients. Receptor-mediated activation of signal transducer and activator of transcription and extracellular signal-regulated kinase pathways in response to cytokine treatments was identified by immunoblot analysis. Thymidine incorporation determined the impact of the cytokines on DNA synthesis. HNNEC and HNSCC displayed a prominent signaling in response to oncostatin M, interleukin-6, IFN-gamma, and epidermal growth factor. Untreated HNSCC showed an elevated level of phosphorylated signal transducer and activator of transcription 3 and extracellular signal-regulated kinase (P < 0.001) compared with HNNEC, suggesting constitutively activated pathways. Moreover, HNSCC cells phosphorylated significantly more signal transducer and activator of transcription 1 in response to oncostatin M (P = 0.002) and IFN-gamma (P = 0.018) treatments. DNA synthesis of SCC cells was less inhibited by cytokines produced by endotoxin-stimulated macrophages (P = 0.016) than that of NEC. Low-dose oncostatin M slightly enhanced proliferation of SCC, whereas that of NEC was suppressed (P = 0.016). This study identified significant alterations in signal transduction pathways engaged by cytokines and which are associated with loss of growth inhibition of HNSCC. Increased signal transducer and activator of transcription phosphorylation, along with constitutively phosphorylated extracellular signal-regulated kinase in HNSCC, suggest that these pathways as molecular markers are important in the malignant transformation process and are potential targets for treatment.

Aged↗
PubMed2003

Pulmonary malignant granular cell tumor.

BACKGROUND: Malignant granular cell tumor (MGCT) is a rare disease entity. Forty-one well-documented MGCTs have been reported in the world literature. CASE REPORT: This report describes a patient who presented with a MGCT of the lung and reviews the preoperative evaluation, pathologic features and differential diagnosis of the disease. This case represents the first report of resected primary pulmonary MGCT. CONCLUSIONS: Diagnosis of MGCT is based on histology of the primary tumor, immunohistochemistry, and exclusion of tumors that may mimic granular cell tumor.

Journal Article↗
PubMed2003

Evaluation of urinary plasminogen activator, its receptor, matrix metalloproteinase-9, and von Willebrand factor in pancreatic cancer.

PURPOSE: Pancreatic cancer remains a devastating problem with the majority of patients succumbing to death from this disease. A hallmark of pancreatic cancer is the loss of basement membrane that may be attributed to the action of urinary plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9). These enzymes are also implicated in angiogenesis. uPA and microvessel density have been shown to be good prognostic indicators for breast and colon cancer. MMP-9 and microvessel density have not been investigated in pancreatic cancer. We have therefore investigated by immunohistochemistry: (a) frequency of uPA expression and its receptor uPAR and the site of synthesis of uPA by in situ hybridization (ISH); (b) MMP-9 and its coexpression with uPA; (c) microvessel density as determined by von Willebrand factor staining and its relationship to uPA and MMP-9 expression; and (d) correlation of these parameters with survival. EXPERIMENTAL DESIGN: Archival paraffin sections of 27 pancreatic tumors were semiquantitatively investigated by immunohistochemistry using the following antibodies: (a) monoclonal antibodies (MAbs) uPA(1) and uPA(2) (3689 and 394, respectively); (b) MAb uPAR, (no. 3932); (c) MAb MMP-9 (no. 936); and (d) rabbit anti-F8RA/vWF. ISH was performed using a uPA cDNA. RESULTS: Both uPA antibodies revealed overexpression of uPA (93%) often with uniform staining of tumor cells. uPAR and MMP-9 showed focal staining in only 52 and 37% of tumors, respectively. Morphologically normal appearing ductal cells in close proximity to tumors overexpressed uPA in contrast to distally located normal cells (P = <0.001). uPA staining was also investigated in pancreatic intraepithelial neoplasia (PanIN) lesions. PanIN 1A/B staining for uPA was seen in 8 cases (30%), that for PanIN 2 in 19 cases (70%), and for PanIN3 in 12 cases (44%). Lumen of microvessels in the tumor stroma also revealed staining of uPA in 10 cases (37%). ISH experiments revealed the presence of uPA mRNA not only in the cytoplasm of tumor cells but also in adjacent normal appearing ducts as well as in PanIN lesions. Patients with overexpression of uPA, uPAR, or MMP-9 had a trend toward poorer survival than those who did not express it. Microvessel density did not show any significant relationship with uPA, uPAR, and MMP-9 expression and survival. CONCLUSIONS: We conclude that uPA and MMP-9 are potential prognostic indicators in pancreatic cancer, whereas microvessel density may not be one. This study confirms our previous observation that uPA is made by the tumor cells themselves. Presence of uPA in vessels of tumor stroma suggests that uPA is in circulation, and its measurement and that of MMP-9 in the blood of these patients may aid in prognosis. Patients showing overexpression of uPA and MMP-9 have a trend toward shorter survival time.

Biotinylation↗
PubMed2003

Thyroid transcription factor-1 expression prevalence and its clinical implications in non-small cell lung cancer: a high-throughput tissue microarray and immunohistochemistry study.

Thyroid transcription factor 1 (TTF-1), a homeodomain-containing transcription factor, plays a pivotal role in lung development, cell growth, and differentiation processes. The current literature reports considerable variation in frequency of TTF-1 protein expression in human non-small cell lung cancer (NSCLC). TTF-1 expression has not been extensively investigated as a prognostic marker in NSCLC. To assess the prevalence of TTF-1 expression, and to evaluate its potential role in disease prognosis, 140 stage I-IIIA NSCLCs with long-term follow-up were studied under uniform conditions using high-density tissue microarray (TMA) combined with immunohistochemistry. Patient survival and association of TTF-1 expression with clinicopathologic parameters were analyzed. One hundred twenty-six tumor samples were fully assessable after tissue processing. Sixty-four samples (50.8%) expressed TTF-1 and 62 (49.2%) displayed no expression. TTF-1 expression was significantly (P < 0.001) correlated with histological subtype: 51 adenocarcinomas (AdCs) (51 of 75; 68%) versus 9 squamous cell carcinomas (SCCs) (9 of 43; 21%) were TTF-1 positive. TTF-1 expression, performance status, nodal status, and tumor stage were significantly related to patient survival. In multivariate analysis, positive TTF-1 expression tended to favor a better patient outcome (P = 0.05). Overall, NSCLC patients with positive TTF-1 expression had a median survival of greater than 57.3 months, whereas those with negative expression had a median survival of 39.4 +/- 5.2 months (log-rank test, P = 0.0067). In this study we found that TTF-1 is predominately expressed in adenocarcinoma. The loss of TTF-1 expression was associated with aggressive behavior of NSCLCs. The results from this study strongly indicate that further investigation is warranted to better define the role of TTF-1 as a prognostic factor in this malignancy.

Adenocarcinoma↗
PubMed2003

Loss of cables protein expression in human non-small cell lung cancer: a tissue microarray study.

Loss of heterozygosity (LOH) on chromosome 18q is common in lung cancer. The genes involved in LOH on 18q in lung cancer have not been well characterized. Cables, a cyclin-dependent kinase (cdk) interacting protein, has recently been identified and mapped to human chromosome 18q11-12. Cables inhibits cell growth and suppresses tumor formation in nude mice, making it a candidate gene for 18q LOH in lung cancer. Little is known regarding Cables protein expression in human non-small cell lung cancer (NSCLC). In this study we examined Cables expression in 163 NSCLC and nonneoplastic lung specimens using tissue microarrays. Strong nuclear staining was present in normal lung and bronchial tissue. We also evaluated the Cables protein expression pattern and its correlation with histopathologic features and with clinical course of NSCLC. The results of the present study demonstrate for the first time that numerous NSCLCs (45%) lose Cables expression. Furthermore, more adenocarcinomas show a loss of this novel protein than do squamous counterparts. The relationship between tumor histology type and Cables expression appears to be statistically significant (P = 0.028). Our results suggest that Cables may be involved in the pathogenesis of NSCLC.

Adenocarcinoma↗
PubMed2003

HER-2/neu protein expression and gene alteration in stage I-IIIA non-small-cell lung cancer: a study of 140 cases using a combination of high throughput tissue microarray, immunohistochemistry, and fluorescent in situ hybridization.

Regarding HER-2/neu expression (gene or protein level) in lung cancer, several studies with inconsistent results have been recently reported, partially due to variable techniques used and/or heterogeneous populations examined. The objective of this study was to examine HER-2/neu expression in a well-defined cohort of non-small-cell lung cancers (NSCLC) and in nonneoplastic lung tissue utilizing a combination of high-density tissue microarray, immunohistochemistry (IHC), and fluorescent in situ hybridization (FISH) under uniform test conditions. One hundred forty stage I-IIIA primary NSCLCs and 38 non-neoplastic lung samples were examined. IHC, using an FDA-approved Hercept monoclonal antibody kit, was performed and HER-2/neu gene alteration was assessed by FISH. The association of expression of HER-2/neu with clinicopathologic parameters was analyzed. Ninety-four percent of tumor samples (131/140) were fully interpretable after tissue processing. Twenty-five of them (19%) overexpressed (2+, 3+) HER-2/neu, while 106 (81%) had no or weak expression. All thirty-four interpretable non-neoplastic lung samples were negative for HER-2/neu alteration at protein and gene level. HER-2/neu protein overexpression correlated well with HER-2/neu gene amplification (r =.83, P < 0.001). HER-2/neu overexpression was significantly associated with histologic subtype: 19 adenocarcinomas (19/82, 23%) versus 4 squamous cell carcinomas (4/44, 9%) overexpressed Her-2/neu (P = 0.04). Statistical significance was observed between HER-2/neu expression and tumor differentiation, with strong positive (3+) expression observed more frequently in poorly differentiated tumors (P = 0.01). Patients with HER-2/neu abnormalities, particularly HER-2/neu gene amplification, exhibited a shorter survival (P = 0.043). The statistically significant difference (P < 0.005) between HER-2/neu alteration in tumor samples(25/131, 19%) and in the nonneoplastic tissue (0/34, 0%) implies that HER-2/neu may have a role in the carcinogenesis of NSCLC. The findings provide evidence supporting the hypothesis that the HER-2/neu receptor may represent a useful molecular target in the treatment of NSCLC. The significant association of HER-2/neu expression and gene amplification with poorly differentiated carcinoma compared with well differentiated carcinoma suggests that HER-2/neu may be involved in NSCLC tumor evolution. Patients with HER-2/neu gene amplification and strong positive expression of HER-2/neu protein showed a strong tendency toward shorter survival.

Adult↗
PubMed2003

Squamous cell carcinoma of the head and neck in nonsmokers and nondrinkers: an analysis of clinicopathologic characteristics and treatment outcomes.

BACKGROUND: The objective of this study was to describe the clinicopathologic manifestations of disease and outcomes of treatment among individuals without a history of smoking tobacco or consuming alcohol who develop head and neck cancer. METHODS: Of 1648 invasive head and neck cancer cases treated between 1970 and 2001 at Roswell Park Cancer Institute, 40 patients were identified as never having smoked tobacco or consumed alcohol during their lifetime. These cases were reviewed to gather data on multiple clinicopathologic variables. RESULTS: Mean age at presentation of nonsmoker/nondrinker head and neck cancer patients was 60 years (range, 27 to 90 years), and 78% (n = 31) of the patients were women. The distributions of tumor sites were 75.0% oral cavity (n = 30), 20.0% oropharynx (n = 8), and 5.0% larynx (n = 2). Sixteen patients (40%) experienced a recurrence of disease during the follow-up period, and 10 patients (25.0%) developed a second primary tumor a median of 6 years after their initial diagnosis. CONCLUSIONS: The nonsmoker/nondrinker head and neck cancer patient tends to be elderly and female, have oral cavity primary tumors, and be predisposed to second primary tumor development.

Adult↗