Prognostic role of serum thymidine kinase 1 kinetics during neoadjuvant chemotherapy for early breast cancer.

BACKGROUND: Emerging data support the use of thymidine kinase 1 (TK1) activity as a prognostic marker and for monitoring of response in breast cancer (BC). The long-term prognostic value of TK1 kinetics during neoadjuvant chemotherapy is unclear, which this study aimed to elucidate. METHODS: Material from patients enrolled to the single-arm prospective PROMIX trial of neoadjuvant epirubicin, docetaxel and bevacizumab for early BC was used. Ki67 in baseline biopsies was assessed both centrally and by automated digital imaging analysis. TK1 activity was measured from blood samples obtained at baseline and following two cycles of chemotherapy. The associations of TK1 and its kinetics as well as Ki67 with event-free survival and overall survival (OS) were evaluated using multivariable Cox regression models. RESULTS: Central Ki67 counting had excellent correlation with the results of digital image analysis (r = 0.814), but not with the diagnostic samples (r = 0.234), while it was independently prognostic for worse OS [adjusted hazard ratio (HRadj) = 2.72, 95% confidence interval (CI) 1.19-6.21, P = 0.02]. Greater increase in TK1 activity after two cycles of chemotherapy resulted in improved event-free survival (HRadj = 0.50, 95% CI 0.26-0.97, P = 0.04) and OS (HRadj = 0.46, 95% CI 0.95, P = 0.04). There was significant interaction between the prognostic value of TK1 kinetics and Ki67 (pinteraction 0.04). CONCLUSION: Serial measurement of serum TK1 activity during neoadjuvant chemotherapy provides long-term prognostic information in BC patients. The ease of obtaining serial samples for TK1 assessment motivates further evaluation in larger studies.

The prognostic value of pre-treatment thrombocytosis in two cohorts of patients with non-small cell lung cancer treated with curatively intended chemoradiotherapy.

Chemoradiotherapy is the standard of care for inoperable stage III non-small cell lung cancer (NSCLC). This treatment, however, offers only a small chance of cure and is associated with many side effects. Little research has been made concerning which patients benefit most/least from the treatment. The present study evaluates the prognostic value of anemia, leukocytosis and thrombocytosis at diagnosis in this treatment setting. In the present study, data were collected retrospectively for 222 patients from two different phase II studies conducted between 2002-2007 in Sweden with patients treated with chemoradiotherapy for stage IIIA-IIIB NSCLC. Clinical data and the serum values of hemoglobin (Hgb), White blood cells (WBC) and Platelets (Plt) at enrollment were collected for all patients and studied in relation to overall survival using Kaplan-Meier product-limit estimates and a multivariate Cox proportional hazards regression model. The results showed that patients with thrombocytosis (Plt > 350 x 109/L) had a shorter median overall survival (14.5 months) than patients with normal Plt at baseline (23.7 months). Patients with leukocytosis (WBC > 9 x 109/L) had a shorter median survival (14.9 months) than patients with a normal WBC at baseline (22.5 months). However, in a multivariate model including all lab parameters and clinical factors, only thrombocytosis and performance status displayed a prognostic significance. In Conclusion, thrombocytosis showed to be an independent prognostic marker associated with shorter overall survival in stage III NSCLC treated with curatively intended chemoradiotherapy. This knowledge can potentially be used together with established prognostic factors, such as performance status when choosing the optimal therapy for the individual patient in this clinical setting.

Hsp90 is expressed and represents a therapeutic target in human oesophageal cancer using the inhibitor 17-allylamino-17-demethoxygeldanamycin.

Heat shock protein 90 (Hsp90) has been demonstrated to protect oncogenic variants of signalling molecules from degradation and may consequently serve as a therapeutic target for the treatment of oesophageal cancer for which adequate therapy is often lacking. We studied the expression of Hsp90 in tumour tissues of human oesophageal cancer and the impact of Hsp90 inhibition on oesophageal cancer cell lines using the drug 17-allylamino-17-demethoxygeldanamycin (17-AAG). Quantitative immunohistochemistry was performed on formalin-fixed paraffin-embedded tissues from patients with oesophageal cancer. In squamous cell carcinoma, a marked upregulation of Hsp90 could be noted in dysplastic epithelium and invasive cancer compared with normal epithelium. In adenocarcinoma, Hsp90 was expressed in neoplastic epithelium and also in normal non-neoplastic glands weakly. The inhibition of Hsp90 using 17-AAG led to a significant decrease in cell proliferation and viability in human oesophageal cancer cell lines. Using a clonogenic cell survival assay, Hsp90 inhibition significantly sensitised the cells for gamma-photon irradiation. Heat shock protein 90 was found to be critical for proper signalling induced by both epidermal growth factor and insulin-like growth factor-1, in which the inhibition of signalling by 17-AAG correlated with the observed reduction in cell proliferation and viability. These results showed that Hsp90 was selectively expressed in oesophageal cancer tissue compared with the corresponding normal tissue, and the inhibition of Hsp90 resulted in decreased proliferation and viability as well as radiosensitisation of oesophageal cancer cells. Heat shock protein 90 represents a potential therapeutic target in the treatment of patients with oesophageal cancer, alone or in combination with radiotherapy.

HER-2 overexpression (3+) in patients with squamous cell esophageal carcinoma correlates with poorer survival.

The incidence of esophageal carcinoma is increasing worldwide. In Sweden, approximately 400 patients are diagnosed each year. The present study retrospectively investigates survival in 97 patients with esophageal carcinoma in regard to their HER-2 status as examined by immunohistochemistry (IHC) and chromogen in situ hybridization (CISH). Sixty-eight patients had localised disease and 29 patients had advanced disease. Seventy patients had squamous cell carcinoma, and nine of these patients (13%) had HER-2 overexpression (3+). Eight (30%) of 27 adenocarcinoma patients overexpressed (3+) HER-2. In patients overexpressing (3+) HER-2 a statistical trend towards poorer survival was observed (P = 0.057). In squamous cell carcinoma patients, HER-2 overexpression (3+) correlated with poorer survival (P = 0.035), whereas in adenocarcinoma patients, HER-2 status (3+) did not. HER-2 amplification according to CISH was present in five (two squamous cell carcinomas and three adenocarcinomas) out of 17 HER-2 overexpressing (3+) tumours. In conclusion, HER-2 overexpression (3+) seems to be associated with poorer survival in esophageal carcinomas, especially in patients with squamous cell esophageal carcinoma.

Role of circulating cytokeratin fragments and angiogenic factors in NSCLC patients stage IIIa-IIIb receiving curatively intended treatment.

Non-small cell lung cancer (NSCLC) is derived from epithelial cells and accounts for approximately 80% of all lung cancers. Cytokeratins are specific for epithelial cells and during malignant transformation the cytokeratin profile usually remains constant. Angiogenesis is the formation of new blood vessels out of the existing vascular bed. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are potent circulating angiogenic factors. The aim of the present study was to determine if increased levels of a new cytokeratin assay (MonoTotal, which in comparison with TPAcyk detects not only fragments of cytokeratins 8 and 18 but also of cytokeratin 19) is correlated with circulating angiogenic factors (VEGF and bFGF) and the secondary aim was to investigate if increased levels of these circulating markers are associated with survival. In the present study, a total of 45 NSCLC patients (26 patients stage IIIa and 19 patients stage IIIb) receiving only curatively intended treatment for advanced NSCLC were included. These patients donated a total of 291 serum samples during follow-up which was investigated for the presence of MonoTotal, VEGF and bFGF. MonoTotal was statistically significantly correlated with bFGF (R=0.26, p=0.00049) and VEGF (R=0.26, p=0.00007). From the time of histological diagnosis until time of death, MonoTotal increased by 603 U/l (p<0.0001). VEGF increased by 430 pg/ml (p=0.0004) whereas the corresponding value for bFGF was 5.93 pg/ml (p=0.018). MonoTotal, a newly developed commercial cytokeratin assay, seems to be a potentially very interesting serum marker that, in conjunction with other clinical data, might be used for monitoring of patients with NSCLC.

Genes associated with telomerase activity levels in esophageal carcinoma cell lines.

Telomerase activity levels have been shown to correlate with tumor progression in several malignancies. However, the genetic regulation of telomerase activity levels is not fully understood. The aim of the present study has been to identify a gene expression profile, predicting correlation with the telomerase-activity test. Ten human esophageal carcinoma cell lines were investigated using the telomerase activity assay (TRAPeze) Telomerase Detection Kit), followed by further characterization using the GeneChip Human Genome U133A 2.0 Array (Affymetrics Inc., USA), including 14 500 human genes. Telomerase activity levels were detected in all cell lines with a broad range of activity levels. Using a high correlation coefficient, r > 0.90, the following genes were found to be positively correlated with telomerase activity levels: N-myristoyltransferase 2; ribosomal protein L3; retinoblastoma-like 2 (pRb2/p130); and cyclin G2. Only one gene was negatively correlated with telomerase activity levels, zinc finger protein 207. In conclusion, the present microarray data provide primary validation data indicating possible candidates for prognostic and prediction factors in esophageal cancer in relation to telomerase activity.

Newly developed assay measuring cytokeratins 8, 18 and 19 in serum is correlated to survival and tumor volume in patients with esophageal carcinoma.

Esophageal carcinoma is the seventh most common cause of cancer-related death in the Western world. In Sweden, approximately 400 new esophageal carcinomas are diagnosed yearly. Cytokeratins (CK) are specific for epithelial cells and the expression profile usually remains unchanged even when the epithelium undergoes malignant transformation. In the present study, MonoTotal, a newly developed RIA-assay detecting circulating CK 8, 18 and 19 fragments, was investigated in sera from patients with esophageal carcinoma. Serum samples from 40 patients with esophageal carcinoma were collected. The median value of circulating CK 8, 18 and 19 measured with MonoTotal was 378 U/L (range 53-6843) and with regard to the defined cut-off (< 75 U/L), 39/40 (98%) patients were shown to have elevated levels of circulating CK 8, 18 and 19. Patients with localized disease had a median value of circulating CK 8, 18 and 19 of 305 U/L (mean: 500 U/L), whereas the corresponding value for metastatic disease was 771 U/L (mean: 1506 U/L). This difference was statistically significant (P = 0.016). Circulating CK 8, 18 and 19, according to cut-off, were not associated with survival in univariate analysis (P = 0.34). However, continuous values of circulating levels of CK 8, 18 and 19 were associated with survival (P = 0.000083) in univariate as well as in the multivariate analysis (P = 0.03). In conclusion, circulating CK 8, 18 and 19 correlates with increased tumor burden and might, in conjunction with other clinical parameters, aid the clinician in estimating the prognosis of the individual patient.

Serum VEGF and bFGF adds prognostic information in patients with normal platelet counts when sampled before, during and after treatment for locally advanced non-small cell lung cancer.

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have both been implicated to have roles in tumour angiogenesis. In the present retrospective study, serum VEGF and bFGF from patients with locally advanced non-small cell lung cancer (NSCLC) were analysed before, during and after treatment. Seventy-three patients and a total of 460 serum samples were analysed for VEGF and 443 serum samples were analysed for bFGF. Pre-treatment bFGF levels in patients with normal platelet counts, were correlated to poorer survival, P-value = 0.047. During chemotherapy, each rise of one unit bFGF corresponded to a hazard ratio of 4.06 (P=0.022). In patients with normal platelet counts, VEGF levels after radiotherapy significantly correlated to good prognosis (P=0.023), during radiotherapy VEGF levels indicated the same correlation (P=0.085). We conclude that serum VEGF and especially bFGF are of clinical interest as prognostic factors, especially in patients presenting with normal platelet counts.

Elevated preoperative serum levels of angiogenic cytokines correlate to larger primary tumours and poorer survival in non-small cell lung cancer patients.

We have analysed the predictive and prognostic information in preoperatively collected serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in patients clinically evaluated as operable non-small cell lung cancer (NSCLC). Fifty-eight patients with operable NSCLC were included. VEGF and bFGF levels in serum were analysed using enzyme linked immunosorbent assays (Quantikine human VEGF and Quantikine HS human FGF basic, R&D Systems). Univariate analysis demonstrated that tumour volume, platelet counts, VEGF and bFGF were significant prognostic factors. However, only bFGF remained significant in the multivariate analysis (P=0.014). Significant correlation's were demonstrated between VEGF levels and tumour volume (r=0.33; P=0.012) and platelet count (r=0.43; P=0.001). bFGF levels correlated significant with recurrent disease (r=0.34; P=0.01), platelet count (r=0.53, P<0.001) and performance status (r=0.29; P=0.029). Furthermore, bFGF levels and VEGF levels correlated significantly (r=0.44; P<0.001). We conclude that elevated circulating angiogenic cytokines correlate with tumour volume, higher relapse risk and poorer survival in patients with operable non-small cell lung cancer.

The frequency of micronuclei in lung cancer cell lines and their correlation to intrinsic radiation sensitivity.

BACKGROUND: Micronuclei arise from chromosomal, acentric, fragments or whole chromosomes that are not incorporated into the daughter nuclei at mitosis. The micronuclei assay is technically simple and requires only one mitosis in order to obtain information concerning the amount of micronuclei. This study was performed to investigate whether the formation of micronuclei could be used as a marker for intrinsic radiation sensitivity in lung cancer patients. MATERIALS AND METHODS: Two human lung cancer cell lines, a non-small cell lung cancer (NSCLC) cell line (U-1810) and a small cell lung cancer (SCLC) cell line (U-1906L), were used. Radiosensitivity data on the survival fraction at 2 Gy were obtained from the clonogenic assay. Radiation was delivered as one-fraction doses: 0, 1, 2, 4, 10 and 20 Gy. After irradiation, the cells were incubated for 0, 24, 48, 60, 72 and 96 hours before fixation and staining. RESULTS: The frequency of micronuclei in U-1906L was clearly elevated after 96 hours in the 20 Gy fraction. The frequency of micronuclei reached 5.5%. For U-1810 the micronuclei had a peak clearly different than the other settings after 48 hours in the 10 Gy fraction. The frequency of micronuclei was 1.2%. CONCLUSION: Counting micronuclei is not sensitive enough for estimation of radiosensitivity in clinical doses. However, our results demonstrated a distinct difference between NSCLC and SCLC cell lines at higher doses. This difference might be due to different repair fidelity, so future studies with this assay should aim to investigate this hypothesis.

Radiation responsiveness of human lung cancer cell lines measured with a short term semiautomatic assay.

BACKGROUND: Fluorometric microculture cytotoxicity assay (FMCA) is a short-term semi-automatic method, based on dye-inclusion of surviving cells. The assay was developed for investigations of drug resistance on tumour cells from biopsy material. In the present study, this short-term assay was evaluated, regarding usefulness in determining radio-sensitivity. MATERIALS AND METHODS: Eight human lung cancer cell lines were used. There were five small cell lung cancer (SCLC and three non-small cell lung cancer (NSCLC cell lines. Results were compared with the corresponding data derived from the clonogenic assay and/or the extrapolation method. RESULTS: The surviving fraction (SF) after 2, 5 and 10 Gy compared with data from the clonogenic assay were not in accordance for 5 of the 8 cell lines. The FMCA assay overestimated SF- values for the SCLC cell lines. CONCLUSION: The FMCA assay is not useful as a quick screening method for the radioresponsiveness in vitro of human tumour cell lines.

Serum p53 autoantibodies as prognostic marker in patients with oesophageal carcinoma.

BACKGROUND: Oesophageal carcinoma is one of the more aggressive cancers and the patients usually seek medical attention only when the disease is already advanced. Therefore it is important to have a tool, which is simple and fast, to measure and to predict the prognosis for these patients. Mutations in the p53 gene are among the most common genetic abnormalities in oesophageal carcinoma. The present study is the first study, to our knowledge, in which the relationship between the presence of p53 autoantibodies in the serum and survival has been investigated in patients with oesophageal carcinoma. PATIENTS AND METHODS: Serum from patients with oesophagal carcinoma was collected between 1996 and 1999 at the Department of Oncology, Uppsala University Hospital, Sweden. The serum samples were analysed for the presence of p53 autoantibodies using a sandwich ELISA. RESULTS: In a multivariate analysis, the presence of p53 autoantibodies was associated with decreased survival (p=0.047). Patients with extensive disease had a poor prognosis and time to death was decreased in these patients (p=0.000022). The one-year survival was 0% for these patients if they had p53 autoantibodies compared to 36% for patients with no p53 autoantibodies and extensive disease. CONCLUSION: We conclude that the presence of serum p53 autoantibodies is associated with decreased survival for patients with oesophageal carcinoma.

Different fraction schedules and combinations with chemotherapy in radiation treatment of non-small cell lung cancer.

BACKGROUND: In locally advanced non-small cell lung cancer (NSCLC), studies demonstrating advantages with hyperfractionated accelerated radiotherapy versus conventional radiotherapy have been published, so have studies demonstrating the value of chemotherapy concomitantly with radiotherapy. However, the value of non-conventional fractionation together with concomitant chemotherapy has not been investigated. MATERIALS AND METHODS: Consecutive patients from a single institution were studied in a retrospective non-randomised fashion. Inclusion criteria were stage III NSCLC, treatment with curative intent and a total dose above 50 Gy. RESULTS: Eighty-two patients were included and further divided into four different treatment groups. Multivariate analysis indicated a survival advantage with non-conventional radiotherapy (NCRT), especially if combined with concomitant chemotherapy. Toxicity was feasible, however there was a trend towards higher toxicity, mainly esophagitis, in patients given concomitant chemotherapy with NCRT. CONCLUSION: Our results suggest that accelerated hyperfractionated radiotherapy with concomitant chemotherapy could be an interesting test-arm in a future prospective study.

Human cytogenetic biomonitoring using flow-cytometric analysis of micronuclei in transferrin-positive immature peripheral blood reticulocytes.

We have developed a method to isolate and analyze nascent human reticulocytes in peripheral blood for the presence of micronuclei (MN). For a very short time peripheral reticulocytes show residual expression of the transferrin receptor. Using immunomagnetic separation of cells expressing the transferrin receptor, a population of immature reticulocytes (Trf-Ret) was isolated from peripheral blood. In humans, the spleen actively removes micronucleated erythrocytes but during the short lifetime of the isolated Trf-Ret only a fraction (less than about 20%) of the MN-containing reticulocytes will have been eliminated. Cells were stained with the fluorescent dyes Thiazole Orange for RNA and Hoechst 33342 for DNA and analyzed by flow cytometry and fluorescence microscopy. Baseline frequencies of MN-Trf-Ret on a group of healthy donors were found to be 1.1% for males and 1.4% for females; however, the gender difference was not significant. The frequency of MN-Trf-Ret in the studied group increased with age, and was dependent on blood group. In three donors studied over 4 months, the baseline level remained stable. In cancer patients treated with radiation or chemotherapy, the frequency of MN-Trf-Ret increased 10- to 20-fold after 1-4 days, depending on the treatment. A high correlation between flow and manual analysis of MN-Trf-Ret was seen. We believe the method has a high potential as a sensitive and rapid method for biological monitoring in presumed exposed groups and individuals.

Cytokeratin 8 and 18 fragments measured in serum and their relation to survival in patients with non-small cell lung cancer.

BACKGROUND: In this study we investigated if the newly developed monoclonal antibodies against Cytokeratin 8 and 18 fragments (Cyk 8/18) have prognostic information in patients with non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Serum from 69 patients with NSCLC was investigated using a sandwich ELISA, Cyk 8/18, provided by IDL Biotech, Sollentuna Sweden. RESULTS: Cyk 8/18 levels varied between 0.34-14.2 ng/mL, compared with a cut-off value of 1.0 ng/mL for healthy individuals (95% specificity). Using that cut-off value, 80% of NSCLC patients had elevated levels. A statistically significant diminished survival was found for Cyk 8/18 values of 8.0 ng/mL or higher (p = 0.0001). When survival data and Cyk 8/18 levels were analysed according to continuous Cox regression analysis, increased levels of Cyk 8/18 were significantly related to decreased survival (p = 0.016). CONCLUSIONS: The Cyk 8/18 monoclonal antibody had in this study prognostic information regarding survival in patients with NSCLC.

Early influence of an ankle sprain on objective measures of ankle joint function. A prospective randomised study of ankle brace treatment.

The purpose of this study was to analyse objective modalities of ankle joint function after an acute ankle sprain and to see whether treatment with an air-cushioned ankle brace could enhance the restoration of function compared with a traditionally used compression bandage. The study included 73 consecutive patients between 15 and 55 years of age with an acute grade II or III ankle sprain, who sought medical care within 24 h of the time of injury. Patients with recurrent sprain were excluded. The patients were allocated at random to treatment with compression bandage or an air-cushioned ankle brace (Air-Stirrup, Aircast). The regimen included early motion and weight-bearing in both groups. The patients were examined initially within 24 h, after 3-5 days, 2, 4 and 10 weeks after the injury by the following tests: clinical examination including range of motion, recording of postural sway by stabilometry, joint position sense test, isokinetic eversion-inversion muscle torques and figure-of-eight running. A decreased active range of motion in eversion-inversion was observed during the entire follow-up period. Increased postural sway was registered when standing on the injured foot up to 4 weeks after the injury, as were a deficit in evertor muscle peak torque and an evertor-invertor muscle imbalance compared with the uninjured side. Women demonstrated a greater impairment in postural sway than men. A longer curve running time with the injured ankle at the outside of the curve was noted at the 10-week follow-up. With the exception of running in a figure of eight, these measures were not influenced by treatment with a semi-rigid ankle brace. The methods used in the present study are well suited for further studies of objective modalities of ankle joint function, with the possible exception of the joint position sense test.

Irradiation of brain metastases from lung cancer: a retrospective study.

A total of 94 patients with brain metastases from lung carcinomas were treated with irradiation of their brain metastases. Two fractionation schedules were applied, a non-conventional one (76 patients) mixing hypofractionation and accelerated hyperfractionation to a total dose of 47 Gy and a conventional one (18 patients), with 3 Gy once a day to a total dose of 30 or 36 Gy. No benefit was found for the non-conventional treatment schedule over the conventional one. A difference in survival was demonstrated between patients whose brain metastases originated from adenocarcinoma or squamous cell carcinoma of the lung with a median survival of 3.5 and 1.9 months, respectively (P = 0.006). Median survival of patients with brain metastases from small cell lung cancer (SCLC) was 2.8 months, and when compared with the squamous cell carcinoma group, there was no statistically improved survival (P = 0.12). There were indications of a better palliative effect in adenocarcinomas compared with squamous or large cell carcinomas. In a few patients (1/22 adenocarcinoma and 7/32 SCLC), the patients were free from malignant cells in the brain at autopsy, demonstrating that irradiation of brain metastases might be efficient in certain patients.

P53 auto-antibodies in non-small cell lung cancer patients can predict increased life expectancy after radiotherapy.

BACKGROUND: In this study we investigated whether the presence of p53 antibodies in sera before of during/after radiation therapy can predict increased survival in patients with non-small cell lung cancer. PATIENTS AND MATERIALS: Sera from 67 patients with a histopathologically confirmed diagnosis of nonsmall cell lung cancer have been investigated using sandwich ELISA (Dianova, Hamburg, Germany). Sera was collected before or during/after radiation therapy. RESULTS: Antibodies were detected in 18 (27%) patients. 46/67 (69%) of the sera had been taken before start of radiation therapy and the presence of p53 antibodies was a statistically significantly good prognostic factor in terms of increased survival (p = 0.025). CONCLUSION: p53 antibodies in sera, before the start of radiation therapy, can predict increased survival after radiation treatment in patients with non-small cell lung cancer.

Basic fibroblast growth factor and vascular endothelial growth factor in sera from non-small cell lung cancer patients.

BACKGROUND: The formation of new microvessels from the existing vascular bed is known as angiogenesis and is normally under the tight regulatory control of angiogenic factors. This control is lost in malignant tumours. Previous studies have correlated increased microvessel density with poor prognosis in patients with primary lung cancer. MATERIALS AND METHODS: Our group measured levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in sera from 68 patients with non-small cell lung cancer (NSCLC) and compared elevated levels of VEGF and bFGF with clinical outcome. Serum basic FGF and VEGF were measured using commercially available enzyme- linked immunosorbent assays (R & D Systems Inc., Minneapolis, MN USA). RESULTS: In 26/68 (38%) patients we found that elevated circulating levels of bFGF and in 27/68 (39%) serum samples levels of VEGF were elevated. Elevated bFGF values in sera was a statistically significant good prognostic factor, p- value = 0.048, when adjusted to stage and there was a trend in that patients with elevated levels of bFGF had a higher fraction of adenocarcinomas compared with squamous epithelial carcinomas (chi 2 = 2.0). No significant correlations could be demonstrated when elevated levels of VEGF in serum was present. Elevated levels of both VEGF and bFGF was present in 45% of the patients. CONCLUSIONS: We found that elevated levels of bFGF is a good prognostic factor when measured in sera from NSCLC patients. As this result disagrees with earlier studies on other malignancies the results from our study needs to be further investigated in a prospective study.

Complete sequence of p53 gene in 20 patients with lung cancer: comparison with chemosensitivity and immunohistochemistry.

In this study the entire p53 complementary DNA has been sequenced in 20 non-small cell lung carcinomas (NSCLC) and the results correlated with chemosensitivity, immunohistochemistry and clinical data. Ten patients had mutations in p53, 8 missense mutations and 2 nonsense mutations. The method discovered two mutations never described previously and two other mutations that have never been described before in connection with NSCLC tumours. Chemosensitivity data, according to a short-term assay (FMCA), indicated that tumours with p53 mutation were more resistant to cisplatin and cyclophosphamide. Immunohistochemical studied demonstrated a 70% concordance between over-expression of p53 protein and mutation in p53. No conclusions or trends could be drawn from the immunohistochemical studies of Bcl-2 and Bax.