Squamous Cell Adenocarcinoma Research Articles

HCGβ expression by cervical squamous carcinoma –in vivo histological association with tumour invasion and apoptosis

To investigate the correlation of beta-subunit of human chorionic gonadotrophin (hCG beta) expression by cervical carcinomas with measures of tumour apoptosis. Eighty-nine cervical carcinoma patients' samples were subject to hCG beta immunohistochemistry and scored with respect to intensity of immunopositivity and percentage of positive cells. Apoptosis was evaluated by three independent parameters: morphological characteristics [haematoxylin and eosin (H&E)], terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling (TUNEL) and poly (ADP-ribose) polymerase (PARP) immunopositivity. Of the 12 adenocarcinomas, only one (8%) was hCG beta+. However, 87% (61/70) of the squamous cell and 100% (7/7) of adenosquamous cell carcinomas were hCG beta+. hCG beta reactivity and intensity was predominantly confined to peripheral tumour cells at the stromal-epithelial interface. Correlation analysis showed that H&E and PARP apoptotic immunopositivity negatively correlated with hCG beta expression (P < 0.001 and P = 0.028 respectively), whereas TUNEL did not (P = 0.12). However, immunopositivity for apoptotic cells by TUNEL was significantly less in tumours where hCG beta expression was greater (scoring >or= 6) and vice versa. hCG beta immunopositivity was also observed in newly formed blood vessels, as well as tumour cells within lymphatic vessels. When tumour vascularization was taken into account, samples with noted vascularization positively correlated with hCG beta scoring. hCG beta expression correlates with reduced tumour cell apoptosis and may be involved in tumour vascularization and dissemination.

Genetic Alteration of Keap1 Confers Constitutive Nrf2 Activation and Resistance to Chemotherapy in Gallbladder Cancer

Biliary tract cancer (BTC) is a highly malignant tumor, and identification of effective therapeutic targets to improve prognosis is urgently required. Oncogenic activation of survival genes is important for cancer cells to overcome oxidative stresses induced by their microenvironments that include chronic inflammation or exposure to anticancer drugs. We attempted to examine whether deregulation of Nrf2, a master transcriptional factor of various cytoprotective genes against oxidative stress, plays a role in the carcinogenesis of BTC. We screened genetic alteration of Keap1, a negative regulator of Nrf2, in BTC including tumors originated from gallbladder and extra- and intrahepatic bile ducts. Functional analysis of cancer-related mutant Keap1 in Nrf2 repression and the association between Nrf2 activation and resistance to 5-fluorouracil (5-FU) were investigated. Recurrent (in 1/11 cell lines and 6/53 primary tumors) Keap1 gene alterations were observed in BTC and were especially frequent (4/13, 30.7%) in gallbladder cancer (GBC). These alterations led to a considerable loss of Nrf2 repression activity, caused constitutive activation of Nrf2, and promoted cell proliferation. Down-regulation of Nrf2 activity by either Keap1 complementation or Nrf2 short interference RNA increased sensitivity to 5-FU in Keap1-altered BTC cells. Keap1 mutation occurs frequently in GBC. Aberrant Nrf2 activation provoked by Keap1 alteration is one of the molecular mechanisms for chemotherapeutic resistance in GBC and will be a novel therapeutic target as an enhancer of sensitivity to 5-FU-based regimens.

Mutations in the LKB1 tumour suppressor are frequently detected in tumours from Caucasian but not Asian lung cancer patients

Somatic mutations of LKB1 tumour suppressor gene have been detected in human cancers including non-small cell lung cancer (NSCLC). The relationship between LKB1 mutations and clinicopathological characteristics and other common oncogene mutations in NSCLC is inadequately described. In this study we evaluated tumour specimens from 310 patients with NSCLC including those with adenocarcinoma, adenosquamous carcinoma, and squamous cell carcinoma histologies. Tumours were obtained from patients of US (n=143) and Korean (n=167) origin and screened for LKB1, KRAS, BRAF, and EGFR mutations using RT—PCR-based SURVEYOR-WAVE method followed by Sanger sequencing. We detected mutations in the LKB1 gene in 34 tumours (11%). LKB1 mutation frequency was higher in NSCLC tumours of US origin (17%) compared with 5% in NSCLCs of Korean origin (P=0.001). They tended to occur more commonly in adenocarcinomas (13%) than in squamous cell carcinomas (5%) (P=0.066). LKB1 mutations associated with smoking history (P=0.007) and KRAS mutations (P=0.042) were almost mutually exclusive with EGFR mutations (P=0.002). The outcome of stages I and II NSCLC patients treated with surgery alone did not significantly differ based on LKB1 mutation status. Our study provides clinical and molecular characteristics of NSCLC, which harbour LKB1 mutations.

Absence of gene mutations in KIT-positive thymic epithelial tumors

Overexpression of KIT, a tyrosine kinase receptor protein encoded by the proto-oncogene c-kit, is observed in human neoplasms such as gastrointestinal stromal tumors (GISTs), myeloproliferative disorders, melanoma and seminoma. In patients with GIST, overexpression of mutated KIT within the tumor is predictive of response to molecular targeted therapy using imatinib. However, the role of KIT expression in thymic carcinoma is not fully understood. Thymic epithelial tumors from 37 patients (17 thymic carcinomas and 20 thymomas) were examined. Immunohistochemical staining with anti-KIT polyclonal antibody and anti-CD5 was performed. Mutation analyses in the juxtamembrane domains, exons 9 and 11, and in the tyrosine kinase domains, exons 13 and 17, were undertaken using polymerase chain reaction (PCR) and direct DNA sequencing in KIT-positive samples. KIT- and CD5-positive staining was observed only in thymic carcinoma. Percentage of positive staining was 100% in squamous cell carcinoma, with no positive staining in other histologies, including atypical carcinoid. Mutation analysis of the KIT gene was performed in 11 squamous cell carcinomas, 1 adenocarcinoma and 1 adenosquamous cell carcinoma. None of the tested samples showed mutations in any of the four exons. Squamous cell carcinoma of the thymus frequently expressed KIT and CD5 proteins, whereas other tumors did not. Unlike GIST, overexpression of KIT does not necessarily indicate gene mutation in thymic carcinoma. KIT and CD5 appear useful for evaluating and subtyping thymic epithelial tumors.

DEK overexpression in uterine cervical cancers

The purpose of the present paper was to investigate the significance of DEK protein expression in uterine cervical lesions and its relationship with HPV infection status. DEK protein expression was studied in 253 cervical lesions, including 30 non-neoplastic cervix with or without squamous metaplasia, 64 cervical intra-epithelial neoplasias (CIN; CIN-1, n = 28; CIN-2, n = 17; CIN-3, n = 19), 102 squamous cell carcinomas (SCC), 51 adenocarcinomas, and six adenosquamous cell carcinomas (adenoSCC) on immunohistochemistry. For comparison, HPV-positive and -negative cervical cancer cell lines were also included. The HPV screening was performed using TaKaRa polymerase chain reaction. On immunohistochemistry DEK was found to be negative in all 30 non-neoplastic cervical epithelia, but it was positive in 96.1% of SCC (98/102), 92.2% of adenocarcinomas (47/51), 100% of adenoSCC (6/6), 85.7% of CIN-1 (24/28), 94.1% of CIN-2 (16/17), and 89.5% of CIN-3 (17/19). There was no significant difference between HPV-positive and -negative cervical lesions. Also, strongly positive staining was observed in all aforementioned cervical cancer cell lines regardless of HPV infection, according to immunocytochemistry. In summary, DEK plays an important role in the carcinogenesis of cervical cancers, and can be helpful for early diagnosis, and is a potential therapeutic target.

Endobronchial metastasis from slow-growing lung cancer: A rare case report and review of the literature

The case of a 36-year-old man with slow-growing lung adenosquamous cell carcinoma and an endobronchial metastasis is reported. Several nodules had been found on a chest X-ray taken 1 year earlier. The same nodules, with no signs of significant progression, were observed during the present admission. A chest computed tomography (CT) image revealed a polypoid lesion in the right intermediate bronchus. Microscopic examination of the polypoid tumor suggested some malignant suspected neoplasm. Therefore, a right intermediate bronchus and right middle and lower lobe lung resection were performed. Histology of the lung nodules revealed an adenosquamous cell carcinoma that closely resembled the endobronchial polypoid tumor. We concluded that the endobronchial tumor was a metastasis of slow-growing lung adenosquamous cell carcinoma. The literature was also reviewed for Japanese patients with endobronchial metastasis who had been treated between 1984 and 2007. Endobronchial metastases originated from 17 different diagnoses of primary malignancies in 90 patients.

HPV+ cervical carcinomas and cell lines display altered expression of caspases

Objective. Loss of expression of apoptotic regulatory proteins in many neoplasias might result in defective or delayed apoptosis, thus facilitating tumor growth or survival. We analyzed here, the basal expression of precursors of apoptotic Caspases in normal cervical epithelium, HPV+ cervical tumor samples and HPV+ tumor-derived cell lines. Methods. Expression of initiator and effector Caspases was analyzed by immunochemistry in normal cervical epithelium and three types of cervical tumors (squamous cell carcinoma, adenocarcinoma and adenosquamous cell carcinoma) whereas expression of Caspases in HeLa, SiHa and CaSki cells was by immunofluorescence, Western blot and RT–PCR. Besides, the effect of the HPV-16 E6/E7 oncogenes on Caspases expression in cervical cells was evaluated by transfecting C33-A (HPV−) cells. Results. Expression of Caspases 3 and 9 was undetectable in adenocarcinoma and adenosquamous cell carcinoma, respectively. Whereas in squamous cell carcinoma, the expression of Caspases was similar those observed in normal samples. Expression of Caspases 3 and 6 was low in HeLa and CaSki cells, while Caspase 8 was low in SiHa and it was not detected in C33-A cells. All Caspases were detected in the cytoplasm and nucleus of the cells. We did not observe an effect of the E6/E7 oncogenes on the expression of Caspases in C33-A cell. Conclusion. Our results showed a differential expression of several Caspases in carcinoma samples and cell lines, suggesting multiple alterations of the Caspase pathways in cervical cancer.

Imaging findings in primary adenosquamous carcinoma of the liver: a case report

Adenosquamous cell carcinoma is characterized by both squamous and glandular components, and is a rare disease of the liver that is the subject of few reports in the literature. We present a case in which the imaging findings on CT, MRI, and hepatic arteriography, as well as pathological correlation of the tumor and the clinical history, aided in including this entity in the differential diagnosis.

Weekly combination chemotherapy of docetaxel and carboplatin and 5-FU in recurrent cervix cancer

16038 Background: The current phase II study assessed docetaxel/carboplatin/5FU given weekly for 24 weeks, for recurrent uterine cervix cancer. Methods: Fourty patients with histologically confirmed, recurrent uterine cervix cancer were enrolled. The patients eligible for this study had histologically confirmed, recurrent uterine cervix cancer. . Patients received weekly docetaxel 20 mg/m2 and carboplatin area under the curve (AUC) 2 weekly with bolus 5FU 500 mg/m2. The response status of the patients was assessed using the common ECOG response criteria. Results: 40 patients were entered in this study. The distribution of intial stage at first presentation was IB, 6 ; IIB, 16; IIIB, 10; IVB, 8. There were 30 squamous cell carcinomas, 6 adenocarcinomas, 4 adenosquamous cell carcinoma. : All patients were evaluable, and completed all planned therapy. The most frequent maximum toxicities during chemotherapy were Grade 2 mucositis with neutopenia. Nonhematological toxicity was generally mild, except for ubiquitous complete alopecia. Responses after 6 months included 6 patients with complete responses, 22 patients with PR and 12 patients with SD. No progression of disease was observed. Conclusions: This regimen was feasible, safe, and particularly well tolerated. Early Phase II outcomes revealed promising activity in patients completing all treatment. No significant financial relationships to disclose.

Adenosquamous/squamous cell carcinoma of the gallbladder

Adenosquamous/squamous cell carcinoma is a rare histopathologic subtype of gallbladder malignancy. Its clinical features have rarely been described, and its differences from the major histopathologic subtype, adenocarcinoma, remain uncertain. All patients with gallbladder carcinoma were retrospectively reviewed. Patients with a histopathologic subtype of either adenosquamous (n = 12) or squamous cell (n = 2) carcinoma were categorized to group I, and patients with adenocarcinoma were categorized to group II. The clinical characteristics and outcomes of these two groups were compared. The two groups were generally no different in clinical features. However, tumor stages of group I patients were significantly advanced (P = 0.048) and included liver involvement (P = 0.008). The outcomes of advanced-stage patients in group II were not different from group I (P = 0.413). Nevertheless, patients in both groups with advanced stage pT who had undergone curative resection showed significantly better survival curves than patients who had undergone non-curative resection (P = 0.003). Patients with adenosquamous/squamous cell carcinoma of the gallbladder were generally similar to those with adenocarcinoma in clinical characteristics, but had a tendency for liver infiltration. Although the two histopathologic subtypes of the gallbladder carcinoma had similar poor outcomes, better survival could be obtained by performing curative resection for these patients.

Anti-tumor effect of bisphosphonate (YM529) on non-small cell lung cancer cell lines

BackgroundYM529 is a newly developed nitrogen-containing bisphosphonate (BP) classified as a third-generation BP that shows a 100-fold greater potency against bone resorption than pamidronate, a second-generation BP. This agent is, therefore expected to be extremely useful clinically for the treatment of osteoporosis and hypercalcemia. Recently, YM529 as well as other third-generation BPs have also been shown to exert anti-tumor effects against various types of cancer cells both in vitro or/and in vivo. In this study, we investigate the anti-tumor effect of YM529 on non-small cell lung cancer (NSCLC).MethodsDirect anti-tumor effect of YM529 against 8 NSCLC cell lines (adenocarcinoma: H23, H1299, NCI-H1819, NCI-H2009, H44, A549, adenosquamous cell carcinoma: NCI-H125, squamous cell carcinoma: NCI-H157) were measured by MTS assay and calculated inhibition concentration 50 % (IC50) values. YM529 induced apoptosis of NCI-H1819 was examined by DNA fragmentation of 2 % agarose gel electrophoresis and flowcytometric analysis (sub-G1 method). We examined where YM529 given effect to apoptosis of NSCLC cells in signaling pathway of the mevalonate pathway by western blotting analysis.ResultsWe found that there was direct anti-tumor effect of YM529 on 8 NSCLC cell lines in a dose-dependent manner and their IC50 values were 2.1 to 7.9 μM and YM529 induced apoptosis and G1 arrest cell cycle with dose-dependent manner and YM529 caused down regulation of phospholyration of ERK1/2 in signaling pathways of NSCLC cell line (NCI-H1819).ConclusionOur study demonstrate that YM529 showed direct anti-tumor effect on NSCLC cell lines in vitro, which supports the possibility that third-generation BPs including YM529 can be one of therapeutic options for NSCLC.

The role of sentinel lymph node detection in vulvar carcinoma and the experiences at the Institute of Oncology Ljubljana

Background. Sentinel node biopsy is a promising diagnostic staging procedure for vulvar carcinoma and it decreases postoperative morbidity. However, it has not been yet approved as a standard procedure. Patients and methods. From March 2003 to the end of 2006, 35 patients were treated for vulvar carcinoma with the technique of sentinel lymph node dissection. Mean age of the patient was 65.8 years (range 36-88 years). There had 32 patients squamous cell carcinoma, one malignant melanoma, one basal cell carcinoma, and one adeno-squamous cell carcinoma. Before surgery, sentinel node biopsy was made with performing 99mTc static and dynamic lymphoscintigraphy and with intradermal injection of methylene blue dye. Results. With this method we haven't found metastases in 25 patients (71.4%). In 3 cases, we failed and found groin recurrence after 12, 24 and 26 months, respectively. In the first, the reason was probably lack of experience, in the second case, we couldn't detect the second active node seen on the lymphographic scan, and in the third case, the reason was a prior surgical procedure and a scar in the groin region. In the group of SNB negative 22 patients were alive at the end of the year 2007 with no evidence of disease, one died after 45 months (groin recurrence), another one died of other causes. For one patient there is no current data. Patient with melanoma malignum is alive with liver metastases. Conclusions. In order to recognize the value of the obtained knowledge about the new treatment method and to confirm the efficiency or inefficiency of this method, further multicenter research studies need to be performed on larger randomized groups of patients.

ΔNp63 protein expression in uterine cervical and endometrial cancers

To investigate the significance of p63 expression in uterine cervical and endometrial cancers. DeltaNp63 protein expression was studied in a variety of 127 cases of uterine cervical lesions (20 non-neoplastic cervices, 43 cervical intraepithelial neoplasia [CIN], 54 squamous cell carcinomas (SCCs), 40 adenocarcinomas, and 13 other histologic types) and 30 endometrioid type of endometrial adenocarcinomas by using immunohistochemistry. One SCC cell line (ME-180) and one adenocarcinoma cell line (HeLa) were also included. In uterine cervix, the expression of DeltaNp63 was increased with progression of CIN, and positive in all SCCs, transitional cell carcinomas, and adenoid basal carcinoma, but negative in all adenocarcinomas. Adenosquamous cell carcinoma and mixed neuroendocrine and squamous cell carcinoma were positive in squamous component, but not in adenocarcinoma and neuroendocrine carcinoma components. ME-180 cell line was positive, whereas HeLa cell line was negative. Endometrioid type of endometrial adenocarcinomas showed a positive staining in glandular (26.7%) and squamous component. Immunohistochemical staining for DeltaNp63 is a powerful marker for squamous differentiation and useful in exclusion of glandular and neuroendocrine differentiation in uterine cervical cancers, but not always in endometrial cancers.

Gender difference in susceptibility to smoking in Korean lung cancer patients having smoking habits

17158 Background: There were some controversies whether women were more or less susceptible to the carcinogenic effect of cigarette smoke and the decline of forced expiratory volume in 1 second (FEV1) to pack-years compared to men. Methods: In this study, we included all lung cancer patients having smoking habits who was histologically diagnosed and performed pulmonary function testing at the time of diagnosis from September 2001 through December 2005. We estimated individual susceptibility to smoking using a formula (SI, susceptibility index) of (100% predicted FEV1)/pack-years. Results: Of 858 lung cancer patients, sex ratio (M/F) was 14.6 (803/55). Past smokers were in 236 (29.3%) for men, 11 (20.0%) for women. Most common hsitologic type was squamous cell carcinoma (477), adenocarcinoma (191), small cell carcinoma (147), adenosquamous cell carcinoma (14), large cell carcinoma (14), NSCLC cell type not specified (15). Pack-years were 41.3 ± 18.9 for men, 29.2 ± 20.4 for women (P = 0.000). FEV1 % was 78.7 ± 23.3 for men, 79.4 ± 22.9 for women (P = 0.832). As for SI, there were no differences between men (0.65 ± 1.1) and women (0.72 ± 1.6) (P = 0.688). Conclusions: Although lung cancer women having smoking habits showed lower pack-years, there were no gender differences in terms of FEV1 decline to cigarette smoking. No significant financial relationships to disclose.

A multi-institutional study of radiation therapy for isolated para-aortic lymph node recurrence in uterine cervical carcinoma: 84 subjects out of over 5,000 population

5052 Background: Most patient who had any recurrent sites of cancer, have been considered to be last-stage of life. However, recent advances of clinical research reveal some patients achieve long-term survival even in recurrence cases. Furthermore, patients who had only one recurrent region, even radiation therapy could play an important role. As for uterine cervical carcinoma, the most common recurrent site other than pelvis is para-aortic lymph node. Furthermore, improvement of diagnostic imaging enables us to detect more frequently isolated para-aortic lymph node recurrence. Thus, we conducted the current study. Methods: Between 1994 and 2003, over 5000 uterine cervical carcinoma patients treated with curative intended treatments at sixteen Japanese major hospitals. Out of them, 84 patients developed para-arotic lymph node recurrence as the only site of initial tumor progression. Seventy-four patitents had squamous cell carcinoma and 5 had adenosquamous cell carcinoma and 5 had adenocarcinoma. These patients were treated with external beam radiation therapy prescribing 1.7–2.0 Gy per fraction, 5 fractions per week and median total dose was 50 Gy (25–60 Gy). Thirty-two patients received adjuvant systemic chemotherapy. Results: Median follow-up time of all patients was 20 months (2–92 months). Three- and 5-year overall survival rates of all patients were 49.5% and 31.3%, respectively. Stratified by patients with or without chemotherapy, 3-year overall survival rate of patients with chemotherapy group was 37.7% and those without group was 56.7% (p = 0.69). Moreover, stratified by symptom sign, 3-year overall survival rate of symptom positive group was 27.6% and those of negative group was 56.1% (p = 0.018). Three-year overall survival rates of the total dose ≥ 51Gy and that of ≤ 50 Gy were 58.0% and 42.8%, respectively (p = 0.07). AS for morbidity, no patients received G3 or greater late toxicity (CTCAE ver. 3.0). Conclusions: The current study suggested that radiation therapy for isolated para-aortic lymph node recurrence in uterine cervical carcinoma could have significant impact on overall survival. Furthermore, no symptom group and over 51Gy irradiation group could achieve better prognosis. No significant financial relationships to disclose.

Prospective analysis of the epidermal growth factor receptor gene mutations in non-small cell lung cancer in Japan

7077 Background: Previous clinical trials have revealed that gefitinib is more likely to be effective in non-small cell lung cancer (NSCLC) with activating somatic mutations of epidermal growth factor receptor (EGFR). Most of those reports evaluated NSCLC patients who had post-operative recurrence and then received gefitinib retrospectively using their surgical specimens. However, many NSCLC patients are inoperable at diagnosis. Thus we conducted this study to examine EGFR mutation status by diagnostic tumor samples before gefitinib treatment and investigate the correlation between EGFR mutation and the efficacy of gefitinib. Methods: We prospectively evaluated various tumor samples obtained from NSCLC patients who had never received gefitinib for EGFR mutations in exon 18–23. For patients treated with gefitinib after the examination of EGFR mutations, the response to gefitinib was also evaluated. Results: From June 2004 to November 2005, 91 patients with advanced or post-operative recurrent NSCLC enrolled onto this study and 104 tumor samples were obtained from transbronchial biopsies, effusions, as well as surgical specimens. Thirty-two mutations including deletions in exon 19 in 23 patients and L858R in 9 patients were detected among those 91 patients; 30 in 81 adenocaricinoma, 1 in 2 adenosquamous cell carcinoma, and 1 in 5 large cell carcinoma. The mutations were found more frequently in female (51.9%) than male (12.8%), in never smoker (52.0%) than smoker (14.6%). Response rate of gefitinib in patients with EGFR mutations was 65.0% (13 of 20) compared to 37.5% (3 of 8) in patients without mutations. Among 7 patients with EGFR mutations who were examined multiple tumor samples, 3 had the discrepancy of EGFR gene status between different samples obtained at different time points, suggesting genetic heterogeneity of their tumors. The EGFR status of the most recent samples is likely to be correlated to the response to gefitinib. Conclusions: The EGFR mutation analysis was possible not only from surgical specimens but also from daily available diagnostic samples. For patients with EGFR mutations, gefitinib could achieve a promising high response rate. We propose to examine the most recent tumor samples to predict the sensitivity to gefitinib reliably. No significant financial relationships to disclose.

Analysis of the VEGF family and their receptors in serum/plasma of patients with pre-invasive and invasive cervical cancer

5016 Background: The vascular endothelial growth factor (VEGF) family and their receptors are essential regulators of angiogenesis and lymphangiogenesis. This study examined the significance of circulating VEGF, VEGF-C, VEGF-D and their receptors VEGFR-1 and VEGFR-2 in patients with preinvasive and invasive cancer in relation to conventional prognostic parameters. Methods: Blood samples were obtained from 125 women before initial treatment (CIN I-III n = 50; FIGO stage I-IV n = 51; relapse n = 24). Plasma (p) and serum(s) levels of pVEGF, sVEGF-D, sVEGFR-1, sVEGFR-2 (R&amp;D Systems, USA) and sVEGF-C (IBL, Japan) were determined by using a quantitative sandwich enzyme-linked immunosorbent assay (ELISA). Results: The highest level of pVEGF (p = 0.007) and sVEGFR-2 (p = 0.014) were detected in patients with recurrent disease, whereas the highest level of sVEGF-D (p = 0.046) were measured in patients with preinvasive lesions (CIN I-III). Furthermore, significantly elevated levels of sVEGF-C (p = 0.021) were detected in early stages (FIGO I-II) in comparison with advanced stages (FIGO III-IV) of cervical cancer. No significant difference in concentration was observed between the various grades of cervical intraepithelial neoplasia (CIN I-III). Correlations between conventional prognostic markers such as lymph node status (N0/N1), lymphangioinvasion (L0/L1), angioinvasion (V0/V1) and grading (G1/G2/G3) were investigated. Increased plasma levels of VEGF (p = 0.036) correlate with the dissemination of tumor cells to regional lymph nodes (N1),whereas serum VEGF-D levels were significantly decreased in women with lymph-node involvement (N1) (p = 0.045) and vascular invasion (L1) (p = 0.019). None of these members of the VEGF family were found to correlate significantly with histological subtype (squamous cell carcinoma, adenocarcinoma, adeno-squamous cell carcinoma) or grading of the tumor cells (G1/G2/G3). Conclusions: These results show that circulating concentrations of VEGF are associated with the stage of disease. In an early stage of cervical cancer a switch to a lymphangiogenic phenotype (VEGF-D, VEGF-C) might be possible. No significant financial relationships to disclose.

Tumor-specific correlation of tumor-type M2 pyruvate kinase (Tu M2-PK) in patients with cervical carcinoma

5044 Background: Pyruvate kinase is a key enzyme in glycosis. Proliferating cells express the tetrameric isoenzyme pyruvate kinase type M2 (M2-PK), which decomposes to the dimeric form during tumor development (Tu M2-PK). This suggests that Tu M2-PK can be used as a tumor marker. The goal of the present study was to investigate the diagnostic value of Tu M2-PK in patients with cervix carcinoma and in patients with preinvasive lesions (CIN I-III). Methods: Plasma samples were investigated from a total of 116 patients using the quantitative sandwich enzyme immunoassay for Tu M2-PK (ScheBo, Tech GmbH). The patients were divided up into 3 groups depending on the severity of their condition: Group 1 (n = 43): CIN I-III; Group2 (n = 49): cervix carcinoma FIGO stage I-IV; Group3 (n = 24): relapse of cervical cancer. Results: The differentiation into three groups depending on the severity of the condition gave significant results, with the group of patients with relapsed cervix carcinoma having the highest concentration of Tu M2-PK (p &lt; 0.001) (mean rank: Group 1 - 33.67, Group 2 - 62.48, Group 3 - 94.85 U/ml). In addition, there was a significant differentiation with respect to the FIGO stage, with increasing concentration for increasing stages (p &lt; 0.001). In contrast with this there was no significant differentiation in patients with preinvasive lesions (p &lt; 0.99). In the evaluation of the correlation with prognosis factors of cervix carcinoma (lymph-node status: N(+), N(−); lymphangioinvasion: L1;L0; angioinvasion: V1, V0 and grading G1–3) there were significantly higher values with positive lymph nodes (N+) (p &lt; 0.0001). No significant differences were determined in the analysis of different tumor sub-types (squamous cell carcinoma, adenocarcinoma, adeno-squamous cell carcinoma) (p = 0.076). Conclusions: These are first results which indicate that Tu M2-PK can be used as a marker to differentiate between malignant and premalignant lesions for patients with cervical cancer. In addition, the concentration correlates with the stage of the disease. No significant financial relationships to disclose.

Bax, bcl-2 and c-kit expression in non-small-cell lung cancer and their effects on prognosis

In non-small-cell lung cancer (NSCLC), stage of the disease is still the most important prognostic factor. Other than stage, many biological markers and many other prognostic factors are studied to define their effects on prognosis of lung cancer. In this study, we aimed to evaluate the expressions of Bax and bcl-2 genes which are important in apoptosis and c-kit, which is a tyrosine kinase transmembrane receptor, as well as searched their response to treatment modalities and effects on survival. Sixty-nine NSCLC cases' pathological samples were stained with specific Bax, bcl-2 and c-kit dyes by immunohistochemical (IHC) methods. IHC evaluation was done by the semichantitative method according to the distribution and intensity of the staining. Twelve of 69 cases (17.4%) were stage I, 28 (40.5%) were stage II, 17 were (24.6%) stage IIIA, nine cases were (13.1%) stage IIIB and three cases (4.4%) were stage IV patients. Their histological subtypes were as follows: of 69 cases, 36 (52.2%) were squamous cell carcinoma, 28 (40.6%) were adenocarcinoma, five (7.2%) were adenosquamous cell carcinoma (two patients) and large-cell carcinoma (three patients). The positive immunostaining rates for Bax and bcl-2 in whole group, squamous cell carcinoma and adenocarcinoma groups were 40.6%/36.2%, 55.6/69.4% and 25.0/0.0%, respectively. The positive immune staining rates for c-kit in whole group, squamous cell carcinoma and adenocarcinoma groups were 7.2, 5.6 and 7.1%, respectively. We didn't find any correlation with Bax, bcl-2 and c-kit expressions and clinicopathological parameters such as age, tumour size, lymph node involvement, smoking, stage of the disease, response to radiotherapy and chemotherapy. Results are interpreted according to survival; bax and bcl-2 expressions were not so effective both in whole group and histologically subgrouped patients. C-kit expression was also found not related with survival in whole group whereas found as a bad prognostic factor in patients with squamous cell carcinoma. These findings could indicate that the expression of apoptotic pathway markers and c-kit may have a role in the prognosis of early stage NSCLC, especially with squamous cell carcinoma subtype.

Prognostic value of the histological subtype in completely resected non-small cell lung cancer

Non-small cell lung cancer (NSCLC), which includes several different histological subtypes, is usually treated by the same strategy. However, the biological behavior of each cell type appears to be different. We retrospectively reviewed the clinical records of 1119 consecutive NSCLC patients who underwent a complete resection, in order to investigate whether a histological cell type is a powerful prognostic factor. The overall 5- and 10-year survivals of the patients with adenocarcinoma (AD), squamous cell carcinoma (SQ), large cell carcinoma (LA), and adenosquamous cell carcinoma (AS) were 54.2 and 40.2%, 51.6 and 30.3%, 40.9 and 18.7%, and 35.1 and 30.1%, respectively. The AD patients had a significantly better survival than the non-AD patients in Stage I (P=0.0004), whereas the SQ patients had a better survival than the non-SQ patients in Stage II (P=0.018). A multivariate survival analysis indicated the AD patients to have a significantly better survival than the SQ patients in Stage IA (P=0.04), while the SQ patients had a better survival than the AD patients in Stage II (P=0.03). These above observations suggest that the prognosis after complete resection is different between adenocarcinoma and squamous cell carcinoma in Stage IA and II.