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Biomedical subjects

Dongfeng Tan

Publications and source records attributed to Dongfeng Tan.

At least 19 recordsLinked to original sources

Autofluorescence bronchoscopy for lung cancer surveillance based on risk assessment.

BACKGROUND: This is a preliminary report of an ongoing prospective bimodality lung cancer surveillance trial for high-risk patients. Bimodality surveillance incorporates autofluorescence bronchoscopy (AFB) and spiral CT (SCT) scanning in high-risk patients as a primary lung cancer surveillance strategy, based entirely on risk factors. AFB was used for surveillance and findings were compared with conventional sputum cytology for the detection of malignancy and pre-malignant central airway lesions. METHODS: 402 patients registering at Roswell Park Cancer Institute were evaluated with spirometric testing, chest radiography, history and physical examination, of which 207 were deemed eligible for the study. For eligibility, patients were required to have at least two of the following risk factors: (1) > or =20 pack year history of tobacco use, (2) asbestos-related lung disease on the chest radiograph, (3) chronic obstructive pulmonary disease with a forced expiratory volume in 1 s (FEV(1)) <70% of predicted, and (4) prior aerodigestive cancer treated with curative intent, with no evidence of disease for >2 years. All eligible patients underwent AFB, a low-dose SCT scan of the chest without contrast, and a sputum sample was collected for cytological examination. Bronchoscopic biopsy findings were correlated with sputum cytology results, SCT-detected pulmonary nodules and surveillance-detected cancers. To date, 186 have been enrolled with 169 completing the surveillance procedures. RESULTS: Thirteen lung cancers (7%) were detected in the 169 subjects who have completed all three surveillance studies to date. Pre-malignant changes were common and 66% of patients had squamous metaplasia or worse. Conventional sputum cytology missed 100% of the dysplasias and 68% of the metaplasias detected by AFB, and failed to detect any cases of carcinoma or carcinoma-in-situ in this patient cohort. Sputum cytology exhibited 33% sensitivity and 64% specificity for the presence of metaplasia. Seven of 13 lung cancers (58%) were stage Ia or less, including three patients with squamous cell carcinoma. Patients with peripheral pulmonary nodules identified by SCT scanning of the chest were 3.16 times more likely to exhibit pre-malignant changes on AFB (p<0.001). CONCLUSION: Bimodality surveillance will detect central lung cancer and pre-malignancy in patients with multiple lung cancer risk factors, even when conventional sputum cytology is negative. AFB should be considered in high-risk patients, regardless of sputum cytology findings.

Adult↗

Leukemoid reaction in pancreatic cancer: a case report and review of the literature.

CONTEXT: The presentation of pancreatic cancer with a leukemoid reaction is rare with no prior reports in the English language literature. CASE REPORT: We report a case of advanced pancreatic cancer presenting with leukemoid reaction. Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor levels were normal while interleukin-6 was elevated. The patient had no evidence of infection. The leukemoid reaction correlated with tumor response. CONCLUSION: This is the first case report in the English literature of a leukemoid paraneoplastic syndrome in a patient with pancreatic cancer. A clear correlation between tumor response, serum carbohydrate antigen 19-9 levels and leukemoid reaction is documented.

Adenocarcinoma↗

Prognostic significance of MCM2, Ki-67 and gelsolin in non-small cell lung cancer.

BACKGROUND: Uncontrolled proliferation and increased motility are hallmarks of neoplastic cells, therefore markers of proliferation and motility may be valuable in assessing tumor progression and prognosis. MCM2 is a member of the minichromosome maintenance (MCM) protein family. It plays critical roles in the initiation of DNA replication and in replication fork movement, and is intimately related to cell proliferation. Ki-67 is a proliferation antigen that is expressed during all but G0 phases of the cell cycle. Gelsolin is an actin-binding protein that regulates the integrity of the actin cytoskeletal structure and facilitates cell motility. In this study, we assessed the prognostic significance of MCM2 and Ki-67, two markers of proliferation, and gelsolin, a marker of motility, in non-small cell lung cancer (NSCLC). METHODS: 128 patients with pathologically confirmed, resectable NSCLC (stage I-IIIA) were included. Immunohistochemistry was utilized to measure the expressions of these markers in formalin-fixed, paraffin-embedded tumor tissues. Staining and scoring of MCM2, Ki-67 and gelsolin was independently performed. Analyses were performed to evaluate the prognostic significance of single expression of each marker, as well as the prognostic significance of composite expressions of MCM2 and gelsolin. Cox regression and Kaplan-Meier survival analysis were used for statistical analysis. RESULTS: Of the three markers, higher levels of gelsolin were significantly associated with an increased risk of death (adjusted RR = 1.89, 95% CI = 1.17-3.05, p = 0.01), and higher levels of MCM2 were associated with a non-significant increased risk of death (adjusted RR = 1.36, 95% CI = 0.84-2.20, p = 0.22). Combined, adjusted analyses revealed a significantly poor prognostic effect for higher expression of MCM2 and gelsolin compared to low expression of both biomarkers (RR = 2.32, 95% CI = 1.21-4.45, p = 0.01). Ki-67 did not display apparent prognostic effect in this study sample. CONCLUSION: The results suggest that higher tumor proliferation and motility may be important in the prognosis of NSCLC, and composite application of biomarkers might be of greater value than single marker application in assessing tumor prognosis.

Aged↗

Genomic instability of human aberrant crypt foci measured by inter-(simple sequence repeat) PCR and array-CGH.

Aberrant crypt foci (ACF) are the earliest identifiable neoplastic lesions in the colon. Thirty-two ACFs were examined for genomic instability in forms detectable either by inter-(simple sequence repeat) PCR or by array comparative genomic hybridization [array-CGH]. One-fourth of ACFs revealed moderate instability by inter-(simple sequence repeat) PCR; none showed amplifications or deletions on array-CGH. The absence of genomic events detectible by BAC array-CGH indicates early events in colorectal tumor progression are typically smaller than the approximate 150 kb size of a BAC clone insert.

Aged, 80 and over↗

Activated Akt and Erk expression and survival after surgery in pancreatic carcinoma.

BACKGROUND: Long-term survival of surgically resectable pancreatic cancer patients is uncommon. The epidermal growth factor receptor (EGFR) and the phosphoinositol-3-kinase pathways are often activated in pancreatic cancer, and an understanding of their role in resected cases may help refine adjuvant therapy. METHODS: We investigated the expression of EGFR, Erk, Akt, and their phosphoforms (p-) in pancreatectomy specimens and correlated these with survival. Thirty-nine consecutive surgically resected pancreatic adenocarcinoma cases were included. Immunohistochemical staining of paraffin-embedded blocks was performed by using monoclonal antibodies against EGFR, Erk, p-Erk, Akt, and p-Akt. A standard immunoperoxidase technique was used to detect the avidin-biotin peroxidase complex. Immunostaining was visually scored with the histoscore method by two surgical pathologists. RESULTS: Patient characteristics were as follows: 17 men and 22 women; median age, 66 years; and American Joint Committee on Cancer stage I, 5 patients; stage II, 4 patients; stage III, 27 patients; and stage IV, 3 patients. The tumor was World Health Organization grade 1 in 4, grade 2 in 17, and grade 3 in 18 cases. Adjuvant therapies were chemotherapy (n = 6), radiotherapy (n = 1), and chemoradiotherapy (n = 17). Immunohistochemistry revealed positive expression of EGFR in 30.8%, Erk in 92.3%, p-Erk in 45.9%, Akt in 71.8%, and p-Akt in 20.5% of cases. On univariate analyses, tumor grade (P = .0098), p-Akt (P = .0003), and p-Erk (P = .0052) expression correlated with survival. On multivariate analyses, age (P = .0002; hazard ratio [HR], 1.8), grade (P = .00318; HR, 3.0), Akt (P = .0433; HR, .4), p-Akt (P = .0002; HR, .2), and p-Erk (P = .0003; HR, 3.5) expression correlated significantly with survival. CONCLUSIONS: p-Erk and p-Akt expression may have prognostic and therapeutic implications in pancreatic cancer.

Adenocarcinoma↗

Inclusion of MUC1 (Ma695) in a panel of immunohistochemical markers is useful for distinguishing between endocervical and endometrial mucinous adenocarcinoma.

BACKGROUND: Distinguishing endocervical adenocarcinoma (ECA) from endometrial mucinous adenocarcinoma (EMMA) is clinically significant in view of the differences in their management and prognosis. In this study, we used a panel of tumor markers to determine their ability to distinguish between primary endocervical adenocarcinoma and primary endometrial mucinous adenocarcinoma. METHODS: Immunohistochemistry using monoclonal antibodies to MUC1 (Ma695), p16, estrogen receptor (ER), progesterone receptor (PR), and vimentin, was performed to examine 32 cases, including 18 EMMAs and 14 ECAs. For MUC1, cases were scored based on the percentage of staining pattern, apical, apical and cytoplasmic (A/C), or negative. For p16, cases were scored based on the percentage of cells stained. For the rest of the antibodies, semiquantitative scoring system was carried out. RESULTS: For MUC1, majority of EMMA (14 of 18 cases, 78%) showed A/C staining, whereas only few ECA (2 of 14, 14%) were positive. The difference of MUC1 expression in the two groups of malignancy was statistically significant (p < 0.001). Staining for p16 was positive in 10 of 14 (71%) ECA and 4 of 18 (22%) EMMA. Estrogen receptor was positive in 3 of 14 (21%) ECA and 17 of 18 (94%) EMMA. Progesterone receptor was positive in 3 of 14 (21%) ECA and 16 of 18 (89%) EMMA. Vimentin was positive in 1 of 14 (7%) ECA, and 9 of 18 (50%) EMA, with median and range of 0 (0-6), and 1.5 (0-9) respectively. CONCLUSION: A panel of immunohistochemical markers including MUC1, p16, ER, PR, and vimentin is recommended, when there is morphological and clinical doubt as to the primary site of endocervical or endometrial origin.

Journal Article↗

Small cell carcinoma of the prostate: an immunohistochemical study.

Small cell carcinoma of the prostate (SCPC) is morphologically similar to small cell carcinoma of the lung (SCLC) and maybe misinterpreted as Gleason pattern 5b prostate adenocarcinoma (HGPC). Recognition of SCPC is important because of its different clinical behavior. This study aims to characterize the immunophenotype of histologically classic SCPC using a comprehensive panel of markers, to better understand its histogenesis, aid in its classification, and evaluate potential therapeutic targets. Using the World Health Organization morphologic criteria for SCLC, 18 SCPC cases were identified; and studied for the following tumor marker groups: prostate specific/related, neuroendocrine, sex steroid hormone receptors, and prognostic/treatment target-related. Ten cases of UPC were used as controls. PSA was positive in 17% of SCPC and neuroendocrine markers were expressed in HGPC. PSA, TTF-1 and CD56 were the most helpful markers in differentiating between SCPC and HGPC (P<0.01), whereas bombesin/GRP, c-kit, bcl-2, and EGFR expression was more frequent in SCPC. SCPC is best diagnosed by following the World Health Organization diagnostic criteria for SCLC. Immunohistochemical markers can help separate SCPC from HGPC and may be useful in histologically borderline cases. Potential therapeutic targets are identified immunohistochemically in SCPC (Bombesin/GRP, c-kit, bcl-2, and EGFR).

Adenocarcinoma↗

Transformation of human bronchial epithelial cells alters responsiveness to inflammatory cytokines.

BACKGROUND: Inflammation is commonly associated with lung tumors. Since inflammatory mediators, including members of the interleukin-6 (IL-6) cytokine family, suppress proliferation of normal epithelial cells, we hypothesized that epithelial cells must develop mechanisms to evade this inhibition during the tumorigenesis. This study compared the cytokine responses of normal epithelial cells to that of premalignant cells. METHODS: Short-term primary cultures of epithelial cells were established from bronchial brushings. Paired sets of brushings were obtained from areas of normal bronchial epithelium and from areas of metaplastic or dysplastic epithelium, or areas of frank endobronchial carcinoma. In 43 paired cultures, the signalling through the signal transducer and activator of transcription (STAT) and extracellular regulated kinase (ERK) pathways and growth regulation by IL-6, leukemia inhibitory factor (LIF), oncostatin M (OSM), interferon-gamma (IFNgamma) or epidermal growth factor (EGF) were determined. Inducible expression and function of the leukemia inhibitory factor receptor was assessed by treatment with the histone deacetylase inhibitor depsipeptide. RESULTS: Normal epithelial cells respond strongly to OSM, IFNgamma and EGF, and respond moderately to IL-6, and do not exhibit a detectable response to LIF. In preneoplastic cells, the aberrant signaling that was detected most frequently was an elevated activation of ERK, a reduced or increased IL-6 and EGF response, and an increased LIF response. Some of these changes in preneoplastic cell signaling approach those observed in established lung cancer cell lines. Epigenetic control of LIF receptor expression by histone acetylation can account for the gain of LIF responsiveness. OSM and macrophage-derived cytokines suppressed proliferation of normal epithelial cells, but reduced inhibition or even stimulated proliferation was noted for preneoplastic cells. These alterations likely contribute to the supporting effects that inflammation has on lung tumor progression. CONCLUSION: This study indicates that during the earliest stage of premalignant transformation, a modified response to cytokines and EGF is evident. Some of the altered cytokine responses in primary premalignant cells are comparable to those seen in established lung cancer cell lines.

Cell Line, Transformed↗

Nuclear or cytoplasmic expression of survivin: what is the significance?

Growing evidence suggests that survivin expression in cancer cell nuclei may represent an important prognostic marker to predict disease outcome for cancer patients. Current reports in this research area, however, are inconsistent and propose opposing conclusions regarding the significance and prognostic value of survivin nuclear expression. The aim of our study is to review and discuss the data reported in the original publications. We have also provided new experimental data to support our view regarding the possible reasons for the observed inconsistencies in the literature. This would alert researchers to pay attention to potential pitfalls in the determination of nuclear or cytoplasmic expression of survivin for the future.

Biomarkers, Tumor↗

Tissue eosinophilia: a morphologic marker for assessing stromal invasion in laryngeal squamous neoplasms.

BACKGROUND: The assessment of tumor invasion of underlying benign stroma in neoplastic squamous proliferation of the larynx may pose a diagnostic challenge, particularly in small biopsy specimens that are frequently tangentially sectioned. We studied whether thresholds of an eosinophilic response to laryngeal squamous neoplasms provides an adjunctive histologic criterion for determining the presence of invasion. METHODS: Eighty-seven(n = 87) cases of invasive squamous cell carcinoma and preinvasive squamous neoplasia were evaluated. In each case, the number of eosinophils per high power field(eosinophils/hpf), and per 10 hpf in the tissue adjacent to the neoplastic epithelium, were counted and tabulated. For statistical purposes, the elevated eosinophils were defined and categorized as: focally and moderately elevated (5-9 eos/hpf), focally and markedly increased(>10/hpf), diffusely and moderately elevated(5-19 eos/10hpf), and diffusely and markedly increased (>20/10hpf). RESULTS: In the invasive carcinoma, eosinophil counts were elevated focally and /or diffusely, more frequently seen than in non-invasive neoplastic lesions. The increased eosinophil counts, specifically >10hpf, and >20/10hpf, were all statistically significantly associated with stromal invasion. Greater than 10 eosinophils/hpf and/or >20 eosinophils/10hpf had highest predictive power, with a sensitivity, specificity and positive predictive value of 82%, 93%, 96% and 80%, 100% and 100%, respectively. Virtually, greater than 20 eosinophils/10 hpf was diagnostic for tumor invasion in our series. CONCLUSION: Our study suggests for the first time that the elevated eosinophil count in squamous neoplasia of the larynx is a morphologic feature associated with tumor invasion. When the number of infiltrating eosinophils exceeds 10/hpf and or >20/10 hpf in a laryngeal biopsy with squamous neoplasia, it represents an indicator for the possibility of tumor invasion. Similarly, the presence of eosinophils meeting these thresholds in an excisional specimen should prompt a thorough evaluation for invasiveness, when evidence of invasion is absent, or when invasion is suspected by conventional criteria in the initial sections.

Journal Article↗

Melanotic schwannoma with drop metastases to the caudal spine and high expression of CD117 (c-kit).

Melanotic schwannomas (MS) are tumors of Schwann cell origin characterized by cytoplasmic deposition of melanin. The authors present the case of a 61-year-old man who experienced progressive weakness of the lower extremities over 2 years. This was followed by acute deterioration, which prompted his presentation. MRI of the spine revealed an intradural, extramedullary lesion at the level of T7 with severe spinal cord compression. More caudally, there was involvement of the lumbar spine with drop metastases to the conus medullaris and cauda equina. The patient underwent thoracic laminectomy for tumor resection. A diagnosis of MS was made based on histologic morphology, immunohistochemical profile, and ultrastructural findings. In this report, the authors describe a MS with expression of CD117 (c-kit) and review the literature pertaining to this condition.

Humans↗

Differential expression of survivin-2B and survivin-DeltaEx3 is inversely associated with disease relapse and patient survival in non-small-cell lung cancer (NSCLC).

Although it was observed that inhibition of the antiapoptotic protein survivin expression in lung cancer cells induces apoptosis, the expression and role of survivin variants (survivin-2B and survivin-DeltaEx3) in lung cancer have not yet been characterized. We analyzed 24 non-small-cell lung cancer (NSCLC) samples by semi-quantitative RT-PCR. Surprisingly, our results revealed that high-level expression of survivin-2B is significantly associated with the patient category of "no relapse and alive" (p-value<0.0001). In contrast, high-level expression of survivin-DeltaEx3 is highly associated with the patient category of "relapse and dead" (p-value<0.0001). Consistent with this observation, exogenous expression of survivin-2B in A549 lung cancer cells inhibited cell growth, disrupted the mitochondria potential, and induced apoptotic cell death, while expression of survivin-DeltaEx3 protected the mitochondria potential and facilitated cell survival. These findings provide evidence that survivin-2B and survivin-DeltaEx3 play opposite roles in disease relapse and NSCLC cell survival, which is likely through the differential modulation of mitochondrial potential. Thus, controlling the differential expression of survivin-2B and survivin-DeltaEx3 may represent novel approaches for cancer therapeutics in NSCLC.

Apoptosis↗

Malignant glomus tumor: a case report and review of literature, focusing on its clinicopathologic features and immunohistochemical profile.

Malignant glomus tumor (MGT) is a rare, recently described neoplasm that recapitulates the appearance of the modified smooth cells of the normal glomus body. We report a case of MGT of the hand of a 48-year-old woman. Magnetic resonance imaging (MRI) showed a 2.8-cm, well circumscribed, enhancing mass on the volar aspect of the thenar region of the right hand in immediate continuity with the ulnar artery and nerve. Computed tomography scan (CT-Scan) of the chest was normal. Histologic evaluation revealed a multilobular lesion with prominent branching capillary vasculature and perivascular arrangement of sheets of tumor cells. The tumor cells were round, relatively uniform in size with distinct cell borders and perinuclear cytoplasmic clearing. They were of intermediate to high nuclear grade and showed significant mitotic activity. A wide local excision with negative margins was performed. Multiple lung metastases were evident at 8-month follow-up. To date, forty-five cases of MGT of skin and soft issue have been reported in the literature. Twelve of the forty-five cases developed metastasis. In this report, we emphasize the differential diagnosis of MGT in the skin and deep soft tissue.

Adenoma, Sweat Gland↗

Interleukin-6 polymorphism is associated with more aggressive prostate cancer.

PURPOSE: : Interleukin-6 (IL-6) has an important role during prostate cancer progression and IL-6 levels in the serum of patients with hormone refractory and metastatic prostate cancer are significantly increased compared with those in patients with hormone sensitive and localized prostate cancer. The G>C polymorphism at position -174 in the promoter of the IL-6 gene has been associated with differences in IL-6 transcription in vitro and IL-6 protein levels in vivo. We determined the association of IL-6 polymorphism with prostate cancer progression. MATERIALS AND METHODS: : We examined the association of IL-6 polymorphism with the risk of advanced disease in 95 patients with different stages of prostate cancer using the tetra-primer polymerase chain reaction genotyping method. RESULTS: : We found that the -174G>C genotype of IL-6 gene was associated with an overall increased risk of advanced prostate cancer. A strong association between this genotype and Gleason score was observed at the -174G>C locus of the IL-6 gene (p <0.001). The distribution of this genotype was also significantly different between stages T3-T4 and T1-T2 tumors (p <0.001). In addition, the IL-6 genotype was linked with vascular invasion (p = 0.024), seminal vesicle involvement (p = 0.006) and capsular invasion (p <0.001). Furthermore, the -174G>C genotype of the IL-6 gene was significantly associated with increased serum prostate specific antigen (p = 0.004) and with recurrent prostate cancer compared with GG homozygotes (p = 0.027). CONCLUSIONS: : These data demonstrate a strong association of the -174G>C polymorphism of the IL-6 gene with the aggressiveness and recurrence of prostate cancer, suggesting that genetic predisposition of genetic differences in the human IL-6 gene could be linked to the risk of recurrent prostate cancer.

Adipose Tissue↗

Retiform hemangioendothelioma: a case report and review of the literature.

BACKGROUND: Retiform hemangioendothelioma (RH) is a rare, recently described vascular neoplasm of low malignant potential. METHODS: We report a case of RH of the foot of a 19-year-old white female. Histologically, the tumor grew as numerous elongated vessels resembling the shape of rete testis with involvement of the skin adnexal structures and subcutaneous adipose tissue. No dissection of collagen by small groups of endothelial cells was seen. Wide local excision was performed and the patient was healthy with no metastasis at 14 months follow-up. RESULTS AND CONCLUSIONS: Our case is discussed in the context of previously reported cases of RH; we also include a review of all cases of RH published to date.

Adult↗

Expression of intestinal trefoil factor (TFF-3) in hepatocellular carcinoma.

BACKGROUND: Trefoil peptides (TFF-1, 2, 3) are a family of protease-resistant regulatory factors that play a role in mucosal restitution, angiogenesis, apoptosis, and tumor progression. Intestinal trefoil peptide (TFF-3) expression has been demonstrated in benign hepatobiliary diseases, but there are limited data regarding its expression in HCC. METHODS: Thirty consecutive cases of HCC from 1998 to 2003 were studied. Immunohistochemistry was performed on formalin-fixed paraffin-embedded blocks of HCC using polyclonal antibody to TFF-3. TFF-3 expression was classified as strong, moderate, weak, focal, and negative. Clinical data were obtained per an IRB-approved protocol. RESULTS: Median age was 69 yr (range: 39-83 yr). Twenty- three patients were males and 7 were females. Treatments included hepatic resection (n = 16), chemo-embolization (n = 4), combined modality therapy (n = 5) and no treatment (n = 4). HCC was well differentiated in 12 (40%), moderately differentiated in 13 (43%), and poorly differentiated in 5 (17%) patients. TFF-3 expression was detected in 28/30 (93.3%) patient samples. Sixteen patients (53%) had moderate and 1 (3%) patient had strong TFF-3 expression. Tumor/ normal tissue interface was assessable in 21 cases; 11 cases expressed TFF-3 at the interface. There was a strong correlation between tumor grade and TFF-3 expression, wherein poorly differentiated tumors had moderate/strong TFF-3 expression (p = 0.008). There was no correlation between TFF-3 expression and survival (p = 0.77). Furthermore, there was no correlation among age, disease stage, and survival. CONCLUSION: TFF-3 is commonly expressed in HCC and its expression correlates with tumor grade.

Adult↗