Primary Lung Squamous Cell Carcinoma Research Articles

Development of Marjolin’s ulcer within one month of burn injury with synchronous primary lung squamous cell carcinoma in an elderly patient: report of a case with allelotyping

Marjolin's ulcer defines the occurrence of malignancy, usually squamous cell carcinoma, in the setting of a post-traumatic scar often following thermal injury. The latency period from the time of injury to the onset of malignant transformation averages 30 years with the earliest documented incidence occurring 6 weeks after injury. In addition, the occurrence of multiple primary malignancies is a rare event. To our knowledge, we report the first case in the literature of a well-differentiated squamous cell carcinoma developing within 1 month of thermal injury to an elderly patient's right index finger with an incidental synchronous primary lung moderately differentiated squamous cell carcinoma that was morphologically and genetically different as confirmed by allelotyping. There is scant precedent literature on acute Marjolin's ulcers, and the most acute cases have arisen 6 weeks post-burn. There is also little published literature on the incidence of multiple primary malignancies. The quoted incidence of this event is <1%. Clinicians should be aware of the possibility of malignant transformation at the site of prior thermal injury. Biopsy remains the gold standard for diagnosis for Marjolin's ulcer. MRI is the most important diagnostic imaging tool because it will demonstrate the margins and extent of the lesion. Due to the aggressive nature of Marjolin's ulcer, treatment is usually surgical and dependent upon grading. When multiple lesions are detected after staging of a presumed neoplasm, the possibility of multiple primary maligancies should be considered. Allelotyping is a process that can be utilized to determine if multiple masses are related.

Gene expression profiling in head and neck squamous cell carcinoma: Clinical perspectives

To date, more than 60 gene expression profiling (GEP) studies have been published in the field of head and neck squamous cell carcinoma (HNSCC) with variable objectives, methods, and results. The purpose of this study was to present a state-of-the-art review of GEP in HNSCC focusing on the current advances and perspectives for clinical applications. Gene expression signatures have been developed to identify screening and diagnostic molecular markers, to improve tumor staging (cervical lymph node and distant metastasis prediction), to differentiate lung metastasis of HNSCC from primary lung squamous cell carcinoma, to predict tumor response to chemoradiotherapy, and to provide outcome predictors. Some transcriptional signatures that could improve HNSCC management have been identified, but further analyses are required to properly validate and to precisely evaluate their clinical relevance. After an exploratory phase, the completion of large scale projects with stringent methodology is now necessary to transfer GEP from bench to bedside.

Expression of CD40, CD86, and HLA-DR in CD1c＋ Myeloid Dendritic Cells Isolated from Peripheral Blood in Primary Adenocarcinoma of Lung

Background: There have been several reports using animal experiments that CD1-restricted T-cells have a key role in tumor immunity. To address this issue, we studied the expression of markers for CD1c＋ myeloid dendritic cells (DCs) isolated from peripheral blood in the clinical setting. Material and Method: A total of 24 patients with radiologically suspected or histologically confirmed lung cancer who underwent pulmonary resection were enrolled in this study. The patients were divided according to histology findings into three groups: primary adenocarcinoma of lung (PACL), primary squamous cell carcinoma of lung (PSqCL) and benign lung disease (BLD). We obtained 20 mL of peripheral venous blood from patients using heparin-coated syringes. Using flow-cytometry after labeling with monoclonal antibodies, data acquisition and analysis were done. Result: The ratio of CD1c＋CD19? dendritic cells to CD1c＋ dendritic cells were not significantly different between the three groups. CD40 (p=0.171), CD86 (p=0.037) and HLA-DR (p=0.036) were less expressed in the PACL than the BLD group. Expression of CD40 (p=0.319), CD86 (p=0.036) and HLA-DR (p=0.085) were less expressed in the PACL than the PSqCL group, but the differences were only significant for CD86. Expression of co-stimulatory markers was not different between the PSqCL and BLD groups. Expression of markers for activated DCs were dramatically lower in the PACL group than in groups with other histology (CD40 (p=0.005), CD86 (p=0.013) HLA-DR (p=0.004). Conclusion: These results suggest the possibility that CD1c＋ myeloid DCs participate in control of the tumor immunity system and that low expression of markers results in lack of an immune response triggered by dendritic cells in adenocarcinoma of the lung.

Cytokeratin expression profiling is useful for distinguishing between primary squamous cell carcinoma of the lung and pulmonary metastases from tongue cancer

It can be difficult to distinguish between primary and metastatic squamous cell carcinoma (SCC) in the lung. Surgical specimens were obtained from two groups of patients, 26 lung SCC patients without histories of any other cancer (the definite primary group) and 17 patients who had undergone surgical removal of SCC emerging in the lung after surgery for tongue SCC (the unknown group). From the former, 26 primary lung SCC were obtained. From the latter, 17 lung tumors and 15 primary tumors of the tongue were obtained. Eleven of the 17 lung tumors from the unknown group were metastatic lung SCC. All specimens were immunostained with cytokeratin (CK)5/6, CK7, CAM5.2, CK19 and p63 antibodies. The frequency of CAM5.2 and CK19 expression was significantly higher in the lung SCC of the definite primary group (21 of 26, 81% and 20 of 26, 78%, respectively) than in the metastatic lung SCC (1 of 11, 9% (P < 0.001) and 2 of 11, 18% (P = 0.003), respectively) or primary SCC of the tongue (5 of 15, 33% (P = 0.002) and 2 of 15, 13% (P < 0.001), respectively). CAM5.2 and CK19 are useful for distinguishing between primary SCC of the lung and metastases from tongue cancer.

Pulmonary Metastasectomy: A Moving Target

For at least 60 years, surgical resection has been a widely used approach to the management of patients with lung metastases from a variety of solid tumors. For many of these patients, surgical resection has provided the only potentially curative treatment. Analyses of numerous retrospective series have led to well-accepted surgical selection criteria: a primary tumor that has been definitively controlled, metastases limited to the lung that can be completely resected, ability of the patient to tolerate the planned operation, and lack of a better alternative treatment. The number of lung metastases, the disease-free interval since treatment of the primary tumor, the tumor doubling time, the presence of lymph node metastases, the histology of the primary tumor, and in some instances, elevated serum markers such as carcinoembryonic antigen are known to influence outcome and may be incorporated into the decision of whether to offer surgery to the patient. However, there remain many controversial aspects to

MiR-21 overexpression in human primary squamous cell lung carcinoma is associated with poor patient prognosis

This study compared miRNA expression patterns in primary squamous cell lung carcinoma specimens with those of matched normal lung tissue in order to determine their potential relevance to clinicopathological factors and patient postoperative survival times. Locked nucleic acids miRNA microarray expression profiling was performed on four matched pairs of tissues. After microarray validation by quantitative real-time reverse transcription polymerase chain reaction assays (qRT-PCR) (real-time PCR), miR-21 was selected for further TaqMan real-time PCR study in 30 matched tissue pairs. Seven miRNAs of hsa-miR-21, hsa-miR-31, hsa-miR-34a, hsa-miR-22*, hsa-miR-504, hsa-miR-18a, and hsa-miR-412 were observed to be upregulated greater than twofold in the squamous cell lung carcinoma tissues compared with normal tissues, whereas 23 miRNAs of hsa-miR-30a, hsa-miR-30d, hsa-miR-126, hsa-miR-652, hsa-miR-100, hsa-miR-143, hsa-miR-130a, hsa-miR-145, hsa-miR-30e, hsa-miR-126*, hsa-miR-181a, hsa-miR-125b, hsa-miR-886-3p, hsa-miR-451, hsa-miR-29c, hsa-miR-26b, hsa-miR-101, hsa-miR-320, hsa-miR-30b, hsa-miR-886-5p, hsa-miR-29a, hsa-miR-26a, and hsa-miR-99a were found to be downregulated greater than twofold. MiR-21 was overexpressed in 73.3% of the squamous cell lung carcinoma specimens examined (P = 0.022). The relationship between the miR-21 expression level and various clinicopathologic factors was also analyzed. High-level expression of miR-21 was significantly correlated with shortened survival time (P = 0.022, log-rank test; Kaplan-Meier). Multivariate Cox proportional hazard regression analysis revealed this significant prognostic impact (P = 0.000; HR 1.293; 95% CI 1.123-1.489) to be independent of clinical disease stage (P = 0.013; HR 2.660; 95% CI 1.229-5.758) and other clinicopathologic factors. Expression patterns of miRNAs were found to be systematically altered in squamous cell lung carcinoma tissue. High miR-21 expression is associated with shortened survival time, indicating that miR-21 may serve as a molecular diagnostic and prognostic marker for patients with squamous cell lung carcinoma.

Expression of OLFM1 protein in lung cancer tissue and its significance

Objective To explore the relationship of OLFM1 expression with the development of lung cancer by comparing the OLFM1 expression in lung cancer specimens and matched normal lung specimens.Methods The OLFM1 mRNA expression was examined by semi-quantitative RT-PCR and fluorescence quantitative PCR in 21 lung cancer tissues and the paired normal lung tissues,and the protein expression of OLFM1 was detected by immunohistochemistry.Results The OLFM mRNA expression levels in 8 primary lung squamous cell carcinoma tissues were decreased by 2.2 folds compared with that in the matched normal lung tissues,with the difference being significantly different(P=0.028).The OLFM1 protein was located in cytoplasm and only expressed in lung adenocarcinoma tissues(P0.001),and the expression was not associated with patients' age,gender,tumor stage,and differentiation degrees(P0.05).Conclusion The lower expression of OLFM1 gene in lung squamous cell carcinoma may serve as a potential molecule marker for the condition.The expression of OLFM1 protein in lung adenocarcinoma,but not in lung squamous cell carcinoma and normal lung tissue,may suggest that different pathological types of lung cancers may have different pathological mechanisms.

Application of 18F-FDG PET/CT in cervical cancer with elevated levels of serum squamous cell carcinoma antigen during the follow-up

Accurate and early diagnosis of recurrence for cervical cancer after the treatment and aggressive salvage treatment could improve the prognosis of this disease. Serum squamous cell carcinoma antigen (SCCAg) is the most commonly used tumor marker for the detection of asymptomatic recurrence of cervical cancer. This study was to evaluate the application and value of (18)F-FDG PET/CT in cervical cancer with elevated of serum SCCAg level during the follow-up. Thirty-one patients with cervical cancer with elevated serum SCCAg level during the follow-up undergoing (18)F-FDG PET/CT in Sun Yat-sen University Cancer Center between August 2005 and November 2008 were entered into this retrospective study. The pathological types, the serum SCCAg level, PET/CT results, results of other imaging modalities, pathological and clinical follow-ups were recorded. All 31 patients'pathological examination showed squamous cell carcinoma, including three adenosquamous carcinoma. Lesions of all patients were examined by PET/CT. Three patients had local recurrence in the uterus or vagina, 28 had metastatic disease. Of these 31 patients, three were confirmed to have local recurrent disease, 27 were verified to have metastatic disease and one was diagnosed as primary lung squamous cell carcinoma by pathological or clinical manifestations. The total detection rate of PET/CT for malignancy was 100% (31/31); the diagnostic accuracy of PET/CT for recurrent cervical cancer was 96.8% (30/31). The levels of serum SCCAg during the follow-up were 1.5-37.8 ng/ml. There was no relation between the level of serum SCCAg and the maximum standard uptake value (SUVmax) of PET/CT. Compared with other imaging modalities, PET/CT was more efficient in detecting recurrence and finding more lesions. An elevated level of SCCAg in cervical cancer during the follow-up indicates tumor recurrence. PET/CT is efficient in detecting the recurrence and has high diagnostic accuracy.

Genomic aberrations in squamous cell lung carcinoma related to lymph node or distant metastasis

About 50% of patients presenting with resectable lung cancer develop distant metastases within 5 years. Genomic markers predicting metastatic behaviour of squamous cell lung carcinoma (SCC) are currently underexposed. We analyzed a cohort of patients with primary SCC using array-based comparative genomic hybridization (aCGH) to identify which genomic aberrations are related to metastatic behaviour. The cohort consisted of 34 patients with a follow-up of at least 5 years, 8 with metastases in regional lymph nodes only and 26 patients without any metastases at the time of surgery. Eleven of the latter 26 developed metastases in distant organs within 3 years after surgery. Copy number changes observed in at least 40% of all SCC included gains at chromosomal arms 3q, 5p, 8q, 19q, 20p, 22q and losses at 3p, 4p, 4q, 5q, 8p and 9p. High copy number amplifications were observed at 2p15-p16, 3q24-q29, 8p11-p12, 8q23-q24, and 12p12, containing candidate oncogenes such as BCL11A, REL, ECT2, PIK3CA, ADAM9, MYC and KRAS. Amplification of 2p15-p16 is a novel finding in SCC. Another novel finding is the homozygous deletion observed at 4q33-34.1 in 15% of the SCC cases. Gains at 7q36, 8p12, 10q22, 12p12, loss at 4p14 and the homozygous deletions at 4q occurred significantly more frequent in SCC from patients with lymph node metastases only. SCC from patients with distant metastases showed a significantly higher gain frequency at 8q22-q24 and loss at 8p23 and 13q21, and a significantly lower gain frequency at 2p12 and 2p16 and loss at 11q25 compared with SCC from patients without metastases. Of these, gains at 7q, 8p and 10q were restricted to SCC with lymph node metastasis and gain at 8q was restricted to patients with distant metastasis. Two genomic aberrations, i.e. loss of 4p and gain of 19q12 were observed more frequently in SCC with only lymph node metastases as compared to SCC with distant metastases. In conclusion, we identified genomic aberrations in primary SCC that were related to lymph node or distant metastases.

Molecular profiling of genes in squamous cell lung carcinoma in Asian Indians

Early metastasis and a poor five-year survival make lung cancer the leading cause of cancer related deaths worldwide. The clinical profile of lung cancer patients in India differs from the West as they present earlier, with squamous cell carcinoma being the commonest histological type. We compared gene expression profiles in primary lung squamous cell carcinoma (LSCC) and matched normal lung tissues in Asian Indians. Using suppression subtractive hybridization, two subtracted cDNA libraries containing differentially expressed genes in the tumors were constructed. Differential expression was confirmed by reverse Northern blot analysis. DNA of confirmed clones was sequenced and subjected to GenBank Blast searches. RNA expression levels were then analyzed by Northern blotting and validated by semiquantitative RT-PCR (in 10 cases of NSCLC). Seventeen differentially expressed gene cDNA fragments of LSCC were analyzed. The differentially expressed genes included those associated with cellular metabolism, cell-cycle, -structure, -adhesion, transcription, proliferation, apoptosis and signal transduction. The study provided first evidence that KIAA0767, a Death Inducing Protein, a novel p53 independent target of E2F1, and Geminin, an inhibitor of DNA replication are differentially expressed in LSCC. Identification of the differentially expressed genes in lung cancer in this study may serve as better molecular markers for early diagnosis and identifying novel intervention sites for anticancer therapy.

Expression of a Peroxisome Proliferator-Activated Receptor γ1 Splice Variant that Was Identified in Human Lung Cancers Suppresses Cell Death Induced by Cisplatin and Oxidative Stress

The activation of peroxisome proliferator-activated receptor gamma (PPAR gamma) has been implicated in the inhibition of tumor progression in lung cancers through the induction of differentiation and apoptosis. Recently, we identified a novel splice variant of human PPAR gamma1 (hPPAR gamma1) that exhibits dominant-negative activity in human tumor-derived cell lines. This study aimed to examine the expression and pathophysiologic roles of a truncated splice variant of hPPAR gamma1 (hPPAR gamma1(tr)) in primary human lung cancer tissues. The expression and localization of hPPAR gamma1(tr) was surveyed in human primary lung cancer tissues using immunohistochemistry and Western blot analysis. Using transfectants stably expressing wild-type hPPAR gamma1 (hPPAR gamma1(wt)) and hPPAR gamma1(tr), we also analyzed the pathophysiologic roles of hPPAR gamma1(tr). We showed that PPAR gamma is expressed predominantly in the nucleus of nontumorous tissues, whereas it is present in both the nucleus and the cytoplasm of tumorous tissues in squamous cell carcinoma (SCC) of the lung. Western blot analysis confirmed the presence of PPAR gamma1(tr) in primary lung SCC tissue but not in nontumorous tissue. Expression of PPAR gamma1(tr) in Chinese hamster ovary cells attenuated their susceptibility to cell death induced by oxidative stress or cisplatin, whereas their susceptibility was completely recovered by down-regulation of PPAR gamma1(tr) with small interfering RNA. hPPAR gamma1(tr) is expressed strongly in tumorous tissues of primary human lung SCC and its overexpression renders transfected cells more resistant to chemotherapeutic drug- and chemical-induced cell death. These data suggest that the decreased drug sensitivity of PPAR gamma1(tr)-expressing cells may be associated with increased tumor aggressiveness and poor clinical prognosis of patients.

Identification and validation of S100A7 associated with lung squamous cell carcinoma metastasis to brain

To identify potential markers associated with non-small cell lung cancer (NSCLC) metastasis to brain, comparative proteome analysis on two lung squamous cell carcinoma (SCC) cell lines, NCI-H226 and H226Br (the brain metastatic cell line of NCI-H226), was performed using two-dimensional electrophoresis (2-DE) followed by a tandem mass spectrometer with a matrix-assisted laser desorption/ionization (MALDI) source. Twenty differential proteins were identified, of which 6 proteins were up-regulated in H226Br cell compared with NCI-H226 cells, whereas 14 proteins were down-regulated. S100A7 and 14-3-3sigma, two of candidate proteins significantly upregulated and downregulated in H226Br cell, were selected to verify the liability of the differential proteins by Western blot. The results were in accordance with 2-D data. To determine whether S100A7 overexpression is actually associated with SCC metastasis to brain, S100A7 protein was testified in 10 brain metastasis tissues from NSCLC, 38 primary NSCLC tissues including half matched local positive lymph nodes, 5 primary brain tumors and 2 non-cancer brain tissues by immunohistochemistry. Of particular interest to us was that the positive staining of S100A7 could be found in 3/5 (60%) brain metastases tissue from SCC and 8/21 (38%) the primary lung SCC tissues, while no positive staining was observed in the brain metastases tissue from Ad (n=5), the primary adenocarcinoma (Ad) tissues (n=17), the primary brain tumors (n=5), all local positive lymph nodes from the primary NSCLC (n=19) and non-cancer brain tissues (n=2). These findings suggest that S100A7 expression is closely associated with SCC metastasis to brain and may be a potential biomarker for monitoring the development of SCC.

Identification of genes differentially expressed in human primary lung squamous cell carcinoma

To identify differentially expressed genes in lung squamous cell carcinomas (SCCs), the suppression subtractive hybridization method (SSH) was performed comparing six lung tumour tissues and 10 morphologically normal bronchial epithelial tissues. A cDNA library consisting of 220 upregulated genes in tumour tissue was established and named as LSCC (lung squamous cell carcinoma). Of them, six were tested using semi-quantitative reverse transcription-PCR on 27 pairs of tumour tissue and normal lung tissue. Differential expression was confirmed in five of these six genes, including IGFBP5, SQLE, RAP2B, CLDN1, and TBL1XR1. The elevated mRNA expression of RAP2B, CLDN1 and TBL1XR1, three genes located on chromosome 3q, were further validated in 64.3% (18/28), 82.1% (23/28), and 75.0% (21/28) of lung SCC tumour tissues, respectively, by quantitative real-time reverse transcription-PCR analysis. Moreover, western blot analysis showed that the protein expression of TBL1XR1 was also upregulated in 53.3% (8/15) of lung SCC tumour samples, as well as in five lung cancer cell lines and in one human immortalized bronchial epithelial cell line. All the initial characteristics of these genes were first reported in the lung SCCs. The differentially expressed genes reported in this study will provide a valuable resource for understanding the pathogenesis of lung SCCs and for discovery of novel diagnostic or therapeutic targets.

Angiogenic Switching in the Alveolar Capillaries in Primary Lung Adenocarcinoma and Squamous Cell Carcinoma

The status of angiogenic switching was examined in alveolar capillaries of primary lung adenocarcinoma (ADC) from 10 patients and primary squamous cell carcinoma (SCC) from 11 patients, using immunostaining for CD31, thrombomodulin, von Willebrand factor (vWF), collagen types IV and VII, and alpha-smooth muscle actin (alpha-SMA). We applied the TdT-mediated dUTP nick-end labeling assay and the reverse transcription-polymerase chain reaction for vascular endothelial growth factor (VEGF) and its receptors (VEGFRs). In bronchioloalveolar and papillary subtypes of ADC, the neoplastic cells, replacing the normal alveolar epithelial cells, had spread over alveolar walls and adhered firmly to alveolar interstitium as shown by the development of type IV collagen. Neoplastic cells of SCC were characterized by local proliferation in alveolar sacs without firm attachment to alveolar walls. Tumor lesions of SCC had often developed necrotic foci of various size. In ADC and SCC, alveolar capillary endothelial cells newly obtained reactivity to vWF. Such segments of endothelial cells lost surface thrombomodulin expression. CD31 was consistently expressed in normal and ADC tissues, but each endothelial cell marker was often attenuated or even lost in SCC, suggesting degeneration or necrosis of the alveolar capillaries. The capillary pericytes and interstitial fibroblasts were often hypertrophic and developed alpha-SMA in the cytoplasm in ADC, but they became atrophic in SCC. In ADC, apoptosis occurred in cells of alveolar capillaries more frequently in the peripheral zone than in the deeper zone of the tumor, whereas the frequency was not consistent in SCC. In microdissected alveolar wall tissues, mRNA expression patterns of VEGF isoforms and VEGFRs were similar in both ADC and SCC. In ADC, de novo angiogenic switching took place in cytoplasm as a unit of cells segments in alveolar capillary endothelium. Suppression of angiogenic switching in SCC implies that factors other than VEGF-VEGFR interaction, such as physical contact and compression of tumor cells, might play a critical role in alveolar capillaries.

Gene expression profiling to distinguish head and neck squamous cell carcinoma metastases from primary lung squamous cell carcinoma

Abstract Introduction: Patients with head and neck squamous cell carcinoma (HNSCC) are at high risk for pulmonary metastasis as well as other primary upper aerodigestive malignancies, most commonly lung squamous cell carcinoma (LSCC). Despite adequate tissue sampling, differentiating a pulmonary nodule with SCC features remains a diagnostic challenge. Our goal was to develop a genomic-based classification that can identify the origin of a lung SCC. Methods: RNA extracted from patients with LSCC (n = 8) and HNSCC (n = 8) was hybridized to oligonucleotide microarrays containing 44363 genes. Novel statistical algorithms identified discriminating genes that prospectively classified 24 patients with HNSCC or LSCC in three unaffiliated institutions (Columbia University, University of Minnesota, University of Pennsylvania). Quantitative PCR and immunohistochemistry confirmed results. Results: Gene expression profiling revealed 65 discriminating genes that can predict LSCC from HNSCC. Genes consistently differentially expressed (p Conclusions: These results demonstrate that gene expression profiling can discriminate primary LSCC from HNSCC tumors and has yielded genes not previously described that have major diagnostic importance. Transcript profiling has revealed pathways in the development of squamous cell carcinoma that may have major significance for future targeted biologic therapies.

CDNA screening to identify genes correlated with SCCRO-associated angiogenesis and metastasis in squamous cell carcinoma of the lung

9549 Background: Lung cancer remains the leading cause of cancer deaths in the United States. We have cloned a novel oncogene - squamous cell carcinoma related oncogene (SCCRO) and established the importance of SCCRO in these tumors. Angiogenesis and metastasis play key roles in the aggressive behavior of SCCRO over-expressing tumors. To investigate these pathways we have developed a novel targeted angiogenesis/metastasis cDNA microarray and corresponding tissue microarray. Methods: Thirty-four previously-untreated patients undergoing resection of primary lung squamous cell carcinomas were selected. SCCRO expression was analyzed using real-time RT-PCR. We identified 277 genes associated with angiogenesis and metastasis based on a comprehensive literature search and constructed a multi-replicate cDNA microarray. RNA was extracted from patient tissue, reverse-transcribed, hybridized, scanned, and normalized. Spotted genes were correlated with SCCRO over-expression. A tissue microarray was constructed using ...

CDNA screening to identify genes correlated with SCCRO-associated angiogenesis and metastasis in squamous cell carcinoma of the lung

9549 Background: Lung cancer remains the leading cause of cancer deaths in the United States. We have cloned a novel oncogene - squamous cell carcinoma related oncogene (SCCRO) and established the importance of SCCRO in these tumors. Angiogenesis and metastasis play key roles in the aggressive behavior of SCCRO over-expressing tumors. To investigate these pathways we have developed a novel targeted angiogenesis/metastasis cDNA microarray and corresponding tissue microarray. Methods: Thirty-four previously-untreated patients undergoing resection of primary lung squamous cell carcinomas were selected. SCCRO expression was analyzed using real-time RT-PCR. We identified 277 genes associated with angiogenesis and metastasis based on a comprehensive literature search and constructed a multi-replicate cDNA microarray. RNA was extracted from patient tissue, reverse-transcribed, hybridized, scanned, and normalized. Spotted genes were correlated with SCCRO over-expression. A tissue microarray was constructed using ...

Squamous cell carcinoma related oncogene regulates angiogenesis through vascular endothelial growth factor-A.

Squamous cell carcinoma related oncogene expression (SCCRO) correlates with vascular endothelial growth factor-A expression. This data is validated in human lung tumors and provides a putative pathway for angiogenesis in a subset of squamous cell carcinomas. Squamous cell carcinoma related oncogene is a novel oncogene identified by positional cloning of a recurrent amplification at 3q26.3. It is over-expressed in 39.8% of lung, head and neck, cervical, and ovarian carcinomas. SCCRO imparts an aggressive phenotype to affected cancers, which may be related to increased angiogenesis due to SCCRO expression. Our previous work has demonstrated a link between SCCRO and vascular endothelial growth factor-A (VEGF-A) expression in vitro, suggesting a mechanism for SCCRO-induced angiogenesis. The present study aims to confirm and validate this link between SCCRO and VEGF-A expression in an ex vivo human tumor cohort. Fresh tissue was collected at Memorial Sloan-Kettering Cancer Center from 34 patients undergoing primary resection of lung squamous cell carcinomas. RNA was extracted from this tissue, reverse-transcribed, and real-time polymerase chain reaction (RT-PCR) was carried out using a BioRad iQ iCycler with SYBR green fluorophore. Microvessel counting was performed on the tumor specimens using CD34 immunohistochemistry. The expression of both SCCRO and VEGF-A mRNA varies widely in both tumor and normal tissue. SCCRO and VEGF-A co-expression was significantly correlated (R(2) = 0.63; P < 0.032). Microvessel counts were not associated with expression of SCCRO or VEGF-A and failed to significantly predict survival. VEGF-A expression in this patient group is a predictor of overall survival (P < 0.032). VEGF-A expression correlates with SCCRO expression in these primary human lung squamous cell carcinomas and is a predictor of clinical behavior. This data supports the association of SCRRO and VEGF-A in the induction of angiogenesis.

Prognostic significance of tumor infiltrating natural killer cells subset CD57 in patients with squamous cell lung cancer

Natural killer (NK) cells have been implied in the resistance against certain tumors and virally-infected cells. The prognostic significance of tumor infiltrating NK cells in primary squamous cell lung carcinoma (SqCLC) has not been fully studied. Fifty patients with primary SqCLC were evaluated for the presence of tumor infiltrating natural killer cells subset CD57 (TINK) after surgery. None of them received adjuvant therapy. Immunohistochemical studies of surgery pieces were performed by using the monoclonal antibody CD57. The number of TINK cells was counted by using a MICRON image analyzer. The total area studied for each tumor was of 1 cm 2. In this area, 50 intratumoral fields of 0.173 mm 2 were selected. The reference value used was the median (five TINK cells/field) of all tumors analyzed. After a minimun follow-up of 2 years the Kaplan–Meier method was used to obtain survival curves. Multivariate analysis were performed by using the Cox regression model. The survival was significantly better in patients with more than five TINK cells/field (Logrank P=0.0317). According to TNM classification, in those patients screened as stage IB (37 patients) the differences in survival were significantly higher (Logrank P=0.0016). In the multivariate analysis including TNM (surgical–pathologic stage), age, and endoscopy localization, the risk of death in patients with less than five TINK cells/field was 2.50 fold higher (CI 95%; range 1.07–5.85) than in those patients with more than five TINK cells/field. These results show that TINK cells appear to be a prognostic factor in the survival of patients with SqCLC. The possible antitumoral role of these cells in SqCLC is discussed.

Metastatic Non-Small Cell Lung Carcinoma With Involvement of Extremity Musculature: Case Report and Review of the Literature

Hematogenous dissemination of non-small cell lung carcinoma (NSCLC) metastatic to skeletal musculature in the absence of osseous involvement is an infrequent occurrence. We retrospectively reviewed our institution's indexed database for patients evaluated from 1975 through 1997 who were diagnosed as having skeletal musculature metastases from NSCLC. Eight men and 2 women were identified (age range, 51-80 years at time of metastases). Four primary adenocarcinomas, 4 primary lung squamous cell carcinomas (SCCs), and 2 poorly differentiated primary NSCLCs were identified. Approximate tumor sizes ranged from 10 cm3 to 288 cm3. External-beam radiation therapy was used in 7 of 10 cases; complete surgical excision was performed in 3 cases. Patients with known neoplasm who have extremity pain and negative findings on bone scan should be evaluated for soft tissue tumor involvement because such findings significantly affect clinical management. One case of lung SCC metastatic to the quadratus femoris muscle in a 63-year-old man is discussed in detail.