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R Rosell

Publications and source records attributed to R Rosell.

At least 91 records · Page 5Linked to original sources
PubMed1997

Reduced survival in patients with stage-I non-small-cell lung cancer associated with DNA-replication errors.

To better understand whether replication-error-type instability (RER+) is a frequent genetic alteration event in surgical-pathologic stage-I non-small-cell lung cancer (NSCLC) and identify whether it constitutes an independent prognostic parameter, we examined 35 surgical-pathologic stage-I-NSCLC patients with complete follow-up in all cases for at least 49 months. The tumor samples and the paired histopathologically normal lung samples for each patient were analyzed for 8 microsatellite markers located at chromosomes 3p and 2p to investigate microsatellite alterations such as RER+ and loss of heterozygosity (LOH). Single-strand-conformation-polymorphism analysis for detection of p53 and k-ras gene mutations was also carried out. Genetic data were correlated with clinical outcome and histopathologically established prognostic factors. RER+ at one or both chromosomes was identified in 24 of the 35 patients; 9 patients showed LOH. A statistically significant correlation was found between RER+ and poor prognosis (p = 0.001). Furthermore, RER+ proved to be an independent factor that predicted decreased survival, ranking first, followed by visceral pleural invasion. A trend towards worse survival was strongest in the group of patients with tumor size greater than 3 cm (T2). Patients with other genetic abnormalities, such as K-ras mutations, p53 mutations or LOH, had prognoses similar to those of patients without such aberrations. The data suggest that RER+ is common in NSCLC, that it may provide important prognostic information in stage-I NSCLC and serve as a useful marker for relapse-risk assessment in operable NSCLC patients.

Adenocarcinoma↗
PubMed1997

[Significance of heterozygosity loss in the long arm of chromosome 5 (5q21) in small cell carcinoma of the lung].

BACKGROUND: Loss of heterozygosity (LOH) at 5q21, where the APC/MCC genes reside, is one of the genetic alterations that characterizes lung cancer. The aim of this study was to analyse LOH frequency on chromosome 5q21 in patients with non-small cell lung cancer and its relationship with TNM staging and histological subtypes. PATIENTS AND METHODS: Tumor and corresponding normal DNA were isolated from 60 patients with non-small cell lung cancer and a subsequent polymerase chain reaction (PCR) with microsatellite markets within the APC/MCC region was performed. The PCR products were resolved by electrophoresis. The comparison between the normal and tumor DNA patterns allowed us to detect the samples harboring LOH. RESULTS: LOH at 5q21 was detected in 20% of the patients. LOH at 5q21 was found in 16% of stage I patients, 8% in stage II patients and 40% in stage IIIA patients. A trend towards worse survival was detected in stage IIIA patients with LOH at 5q21 (9 months median time survival) in comparison with patients with LOH (21 months), although the difference was not statistically significant (p = 0.11). No significant differences in LOH were observed among histological types. In addition, we found no correlation between LOH and higher frequency of mutations rate affecting K-ras and p53 genes. CONCLUSIONS: LOH at 5q21 is a frequent genetic alteration in non-small cell lung cancer and correlates with locally advanced disease (stage IIIA). Our results suggest that LOH at the 5q21 region could be a prognostic factor in non-small cell lung cancer.

Carcinoma, Non-Small-Cell Lung↗
PubMed1997

Serum anti-p53 antibodies and prognosis of patients with small-cell lung cancer.

BACKGROUND: Some patients with cancer develop antibodies against the p53 tumor suppressor protein. The presence of these antibodies in serum has been associated with the expression of mutant p53 by the tumor and in some studies with a poorer survival. PURPOSE: The goals of this study were to determine the prevalence of anti-p53 antibodies in the serum of patients with newly diagnosed small-cell lung cancer (SCLC) and to assess the clinical relevance of the presence of these antibodies in the serum, particularly their relationship with tumor response to treatment and with patient survival. METHODS: In this prospective study, serum was obtained from 170 patients at the time of diagnosis of SCLC who were to subsequently receive platinum- or doxorubicin-based chemotherapy at any one of four hospitals in Barcelona, Spain, from October 1991 through June 1994. Normal human sera from blood bank donors (n = 50) served as controls. The presence of anti-p53 antibodies was determined by western blot analysis with the use of purified recombinant p53 protein. As of January 1996, 96.5% of the patients had been treated and observed in the study, for a median follow-up time of 33.5 months. Survival was estimated by the Kaplan-Meier method. Cox proportional hazards regression and unconditional logistic regression analyses were conducted. All P values resulted from two-sided tests. RESULTS: Anti-p53 antibodies were detected in the serum of 27 (16%) of the 170 patients studied. None of 50 serum samples from normal individuals contained anti-p53 antibodies. Analysis of pretreatment clinical characteristics demonstrated that a weight loss of less than 5% (P = .025), a serum lactic acid dehydrogenase (LDH) level of less than 450 U/L (P = .002), and limited stage disease (i.e., tumor confined to one hemithorax, with local and regional lymph node positivity for tumor cells and/or ipsilateral pleural effusion allowed) (P < .001) were associated with a statistically significant complete response to therapy. The presence of serum anti-p53 antibodies was not associated with clinical characteristics, such as age (P = .622), functional status (P = 1.0), disease stage (P = .634), complete response to treatment (P = .572), and survival (P = .492) or with any laboratory parameters including known prognostic factors in SCLC, such as serum sodium or LDH concentration (P values of .731 and .246, respectively). CONCLUSIONS AND IMPLICATIONS: The presence of anti-p53 antibodies in the serum of patients with newly diagnosed SCLC was not associated with any clinical characteristics or prognostic markers, suggesting that, in this context, the measurement of anti-p53 antibodies is not a useful prognostic marker.

Aged↗
PubMed1997

Modified weekly regimen with vinorelbine as a single agent in unresectable non-small cell lung cancer.

After a 26% response rate was reported with a 20/mg/m2/week vinorelbine (VRL) dose, a multicenter phase II trial of a modified weekly VRL treatment protocol (30 mg/m2 days 1 and 8 every 21 days) for unresectable non-small cell lung cancer (NSCLC) was designed to determine its clinical activity, toxicity, and survival of treated patients. As myelotoxicity frequently precludes the administration of VRL, by suppressing the dose that would correspond to day 15 of a weekly protocol, we allowed bone marrow recovery to take place and avoided the administration of the drug at the nadir of the cycle. The trial included 71 consecutive, previously untreated patients with unresectable and measurable disease. A total of 297 three-week treatment courses were administered with an average of 4 courses per patient (range 1-11). Results showed that in spite of attaining a median dose intensity of 19 mg/m2/week, this modified weekly VRL treatment regimen has a low level of activity (7.5% response rate) in NSCLC. Although a more tolerable level of toxicity is achieved, in order to maintain its antitumor activity, the recommended dose of VRL when given alone for NSCLC treatment (30 mg/m2/weekly) should not be decreased.

Adult↗
PubMed1997

Combination of oral idarubicin and prednimustine in advanced breast cancer: a phase II study.

The aim of this study was to assess the efficacy and toxicity of an idarubicin-prednimustine combination in advanced breast cancer. 19 patients received idarubicin 35 mg/m2 day 1 and prednimustine 100 mg/m2 days 2-6, every 21 days. Three objective responses with a median duration of 7 months were observed. Tolerance was good. A further 23 patients were given idarubicin administered at 15 mg/m2 days 1, 2 and 3 and prednimustine at the aforementioned dosage. 8 (35%) showed an objective response (4 CRs, 4 PRs) with a median duration of 6 months. No severe toxicity was observed. Results suggest activity of idarubicin-prednimustine combinations in advanced breast cancer, and further studies are indicated since this regimen is easily administered, especially to elderly patients.

Administration, Oral↗
PubMed1997

Prognostic value of replication errors on chromosomes 2p and 3p in non-small-cell lung cancer.

As chromosomes 2p and 3p are frequent targets for genomic instability in lung cancer, we have addressed whether alterations of simple (CA)n DNA repeats occur in non-small-cell lung cancer (NSCLC) at early stages. We have analysed by polymerase chain reaction (PCR) assay replication errors (RER) and loss of heterozygosity (LOH) at microsatellites mapped on chromosomes 2p and 3p in 64 paired tumour-normal DNA samples from consecutively resected stage I, II or IIIA NSCLC. DNA samples were also examined for K-ras and p53 gene mutations by PCR-single-stranded conformational polymorphism (PCR-SSCP) analysis and cyclic sequencing, as well as their relationship with clinical outcome. Forty-two of the 64 (66%) NSCLC patients showed RER at single or multiple loci. LOH was detected in 23 tumours (36%). Among patients with stage I disease, the 5-year survival rate was 80% in those whose tumours had no evidence of RER and 26% in those with RER (P = 0.005). No correlation was established between RER phenotype and LOH, K-ras or p53 mutations. RER remained a strong predictive factor (hazard ratio for death, 2.89; 95% confidence interval, 2.23-3.79; P = 0.002) after adjustment for all other evaluated factors, including p53, K-ras, LOH, histological type, tumour differentiation and TNM stage, suggesting that microsatellite instability on chromosomes 2p and 3p may play a role in NSCLC progression through a different pathway from the traditional tumour mechanisms of oncogene activation and/or tumour-suppressor gene inactivation.

Adult↗
PubMed1997

Preoperative chemotherapy for stage IIIA non-small cell lung cancer.

Recent studies have shown that preoperative chemotherapy is feasible and advisable for patients with stage IIIA mediastinoscopically confirmed N2 involvement in non-small cell lung cancer. Such studies confirm the crucial pillar of attaining complete resection, and the importance of downstaging N2 disease as a useful surrogate for long-term survival. Resectability rate is about 70% in almost all studies examined. Better means of predicting resectability and relapse are addressed, such as the potential role of positron emission tomography and some hints for the management of replication error-positive non-small cell lung cancer patients. A major issue for the role of preoperative chemotherapy is how not to confuse apples and oranges. Although the role of surgery alone or radiotherapy is considered suboptimal for treatment of stage IIIA N2, whether surgery is required remains to be clarified. Furthermore, large randomized studies of chemoradiation followed by surgery versus chemoradiation alone are needed as well as modification of the current tumor, node, metastasis classification in order to better select those patients for whom preoperative chemotherapy would be beneficial. The surgeon's judgment and skill are essential in the identification of eligible patients and multimodality treatment research is also spreading toward early disease and some subsets of T4 non-small cell lung cancers.

Biomarkers↗
PubMed1997

Anti-Hu antibodies in patients with small-cell lung cancer: association with complete response to therapy and improved survival.

PURPOSE: Anti-Hu antibodies (HuAb) recognize antigens expressed by neurons and small-cell lung cancer (SCLC). High titers of HuAb were initially reported in serum from patients with paraneoplastic encephalomyelitis/sensory neuropathy (PEM/SN) and SCLC. Preliminary studies have indicated that some SCLC patients without PEM/SN harbor low titer of HuAb in their serum, and that the SCLC of these patients may grow more indolently. Based on these observations, we conducted a multicenter prospective study of SCLC patients without PEM/SN to determine the incidence and prognostic implications of HuAb. METHODS: Serum samples were collected at diagnosis of SCLC in 196 patients without PEM/SN. HuAb were determined by immunoblot of purified recombinant HuD antigen. RESULTS: HuAb were detected in 32 (16%) of the 196 patients. Of the 170 patients who received treatment for the tumor, 27 (16%) were HuAb positive. HuAb was associated with limited disease stage (59.3% v 38.6%; P = .047), complete response to therapy (55.6% v 19.6%; P < .001), and longer survival (14.9 v 10.2 months; P = .018). In a logistic regression analysis, HuAb status was an independent predictor of complete response induction. The probability of achieving a complete response was more than five times higher in HuAb-positive than in HuAb-negative patients (odds ratio, 5.4; 95% confidence interval, 1.71 to 16.89; P = .004). Cox multivariate analysis indicated that HuAb status was not independently associated with survival. CONCLUSION: The presence of HuAb at diagnosis of SCLC is a strong and independent predictor of complete response to treatment. This feature accounts for the association between HuAb and longer survival.

Antibodies, Neoplasm↗
PubMed1997

A sequence-dependent paclitaxel/etoposide phase II trial in patients with non-small cell lung cancer.

Studies conducted by the Spanish Lung Cancer Group indicate that cisplatin- or carboplatin-based chemotherapy can yield a 25% response rate, 9-month median survival time, and 30% 1-year survival rate in patients with stage III and IV non-small cell lung cancer. Phase II trials of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) have an almost 30% response rate in non-small cell lung cancer. Based on these results, we decided to examine whether the sequence-dependent effects of paclitaxel/etoposide influence treatment outcome (antitumor response) and toxicity. In vitro data show a paradoxical antagonist rather than additive effect. In the first part of our study (part A), paclitaxel and etoposide were administered at the same time. In the second part (part B), etoposide preceded paclitaxel. In both parts, patients with previously untreated stage IIIB or IV non-small cell lung cancer with good performance status were eligible. In part A, etoposide (fixed dose, 100 mg/m2) on days 1, 2, and 3 was administered by 30-minute infusion; paclitaxel (175 mg/m2) was given by a 3-hour infusion on day 1. In part B, the etoposide dose and schedule were the same, but paclitaxel (same dose) was administered on day 4. Treatment in both parts was repeated every 21 days for a maximum of 10 cycles. In part A, 18 patients were entered and no objective responses were observed. In part B, 21 patients were accrued, 17 of whom had sufficient follow-up for response assessment. Seven objective responses were achieved (two complete and five partial responses, for an objective response rate of 41%). Seven patients had no change and three had progressive disease. Frequency and severity of side effects were not significantly different in either part of the study. However, grade 4 neutropenia was observed in 10 (59%) patients and one (5%) patient in parts A and B of the trial, respectively. Nonhematologic toxicity was slight. In conclusion, paclitaxel cytotoxicity is abrogated when it is given concurrently with etoposide. When etoposide precedes paclitaxel, a more effective paclitaxel/etoposide schedule is attained.

Adult↗
PubMed1997

Microsatellite alterations at 5q21, 11p13, and 11p15.5 do not predict survival in non-small cell lung cancer.

We investigated the clinical implications of allelic deletions at three common sites of loss of heterozygosity (LOH) in regions 5q21, 11p15.5, and 11p13 in 86 patients with non-small cell lung cancer (NSCLC). We performed a PCR-based microsatellite polymorphism assay for detection of LOH. The microsatellite markers used were D5S82 (proximal to the APC gene), MCC (within the MCC gene), D11S904 (11p13), HRAS (within the H-ras gene), and D11S860 (11p15.5). Of the 68 informative cases at 5q21 loci, LOH was found in 14 cases (20%), whereas LOH frequency in 11p15.5 and 11p13 was 31% (19 of 61 informative cases) and 19% (12 of 63 informative cases), respectively. There was a significant correlation between 5q21 LOH and mediastinal lymph node involvement (P = 0.03). However, no differences were observed in median survival times (26 months in patients with 5q21 LOH versus 37 months in the remainder; P = 0.33) nor in patients with 11p LOH (38 months versus 32 months, respectively; P = 0.72). Cox's proportional hazards model predicted that stage was the only independent poor prognostic marker in the entire cohort of NSCLC patients. Thus, the present study revealed two important abnormalities, LOH at chromosome 5q21 and LOH at chromosome 11p, both implied in NSCLC development.

Adult↗
PubMed1996

Phase II study of mitonafide in non-small cell lung cancer (NSCLC).

BACKGROUND: The new intercalative agent Mitonafide was shown in early clinical trials to be toxic to the central nervous system when administered as a short intravenous infusion, but not when given as a 120-hour continuous infusion. Thus, clinical development in different tumor types was pursued using only this administration schedule. PATIENTS AND METHODS: Forty-nine patients with previously untreated non-small cell lung cancer (NSCLC) and at least one measurable site received Mitonafide as a 120-hour continuous (5 days) infusion every 3 weeks. The starting dose was 170 mg/m2/day x 5 in the first 26 patients and 200 mg/m2/day x 5 in the remainder. Patients were evaluated for toxicity after each course and for response every two courses and remained on treatment until excessive toxicity or disease progression were observed. A special test, the "Mini-mental state", was used to assess patients' cognitive functions. RESULTS: Of the 49 patients entered, 42 were evaluable for response and toxicity. Toxicity consisted mainly of myelosuppression and no neurologic side effects were observed. Only one patient presented a partial response. CONCLUSIONS: Although definitively safe with this schedule of administration, Mitonafide is not active in NSCLC.

Adult↗
PubMed1996

The role of induction (neoadjuvant) chemotherapy in stage IIIA NSCLC.

Induction (neoadjuvant) chemotherapy has become an accepted treatment for stage IIIA (T1-3N2M0) non-small cell lung cancer. In two recent randomized trials, neoadjuvant chemotherapy plus surgery gave an increase in median survival at least fivefold greater than surgery alone. The Spanish Lung Cancer Group trial of preoperative chemotherapy, in which the cisplatin dose was randomized to either 50 mg/m2 or 100 mg/m2 plus 3 g/m2 ifosfamide and 6 mg/m2 mitomycin, examines the effect of K-ras gene mutations on tumor response and survival. Patients whose tumors contain K-ras gene mutations are more likely to develop distant metastases and have lower median survival than patients without such mutations. Microsatellite instability seems to be a frequent mechanism of genetic aberrations. Knowledge about these genetic alterations could have prognostic importance and may identify the patients who should receive the most aggressive additional treatment.

Carcinoma, Non-Small-Cell Lung↗
PubMed1996

Upper extremity deep venous thrombosis in cancer patients with venous access devices--prophylaxis with a low molecular weight heparin (Fragmin).

Central venous access devices are often essential for the administration of chemotherapy to patients with malignancy, but its use has been associated with a number of complications, mainly thrombosis. The true incidence of upper extremity deep vein thrombosis (DVT) in this setting is difficult to estimate since there are very few studies in which DVT diagnosis was based on objective tests, but its sequelae include septic thrombophlebitis, loss of central venous access and pulmonary embolism. We performed an open, prospective study in which all cancer patients who underwent placement of a long-term Port-a-Cath (Pharmacia Deltec Inc) subclavian venous catheter were randomized to receive or not 2500 IU sc of Fragmin once daily 90 days. Venography was routinely performed 90 days after catheter insertion, or sooner if DVT symptoms had appeared. Our aims were: 1) to investigate the effectiveness of low doses of Fragmin in preventing catheter-related DVT; and 2) to try to confirm if patients with high platelet counts are at a higher risk to develop subclavian DVT, as previously suggested. On the recommendation of the Ethics Committee, patient recruitment was terminated earlier than planned: DVT developed in 1/16 patients (6%) taking Fragmin and 8/13 patients (62%) without prophylaxis (Relative Risk 6.75; 95% CI: 1.05-43.58; p = 0.002, Fisher exact test). No bleeding complications had developed. As for prediction of DVT, there was a tendency towards a higher platelet count in those patients who subsequently developed DVT, but differences failed to reach any statistical significance (286 +/- 145 vs 207 +/- 81 x 10(9)/1; p = 0.067). According to our experience, Fragmin at the dosage used proved to be both effective and safe in these patients.

Adult↗
PubMed1996

Radiolocalization of squamous lung carcinoma with 131I-labeled epidermal growth factor.

Overexpression of epidermal growth factor receptor (EGFr) in squamous carcinomas has been demonstrated extensively. Preliminary clinical studies have shown that radiolabeled anti-EGFr monoclonal antibodies can localize to these tumors. The aims of this study were to determine the tolerance, pharmacokinetics, and radiolocalization properties of 131I-labeled EGF in patients (n = 9) with advanced squamous lung cancer. Patients' vital signs and symptoms were monitored regularly for 3 days. Daily scintigrams and biological samples for pharmacokinetic analysis were obtained for 3-4 days. 99mTc-labeled human serum albumin was administered to patients with positive tumor scans. Six patients had positive tumor scans, and five of them had received >/=1.0 mg EGF. In all of these cases, tumors were visualized the same day of the infusion, although best tumor-background contrast was obtained at 50-74 h. There were no false-positive images. Whole-body radioactivity retention rose significantly with increasing EGF doses; most labeled EGF was eliminated by urinary excretion. Tumor:normal tissue uptake ratios increased during the course of the study. All patients presented self-limited, dose-related gastrointestinal adverse effects. In conclusion, recombinant 131I-labeled EGF administered i.v. can localize to squamous lung cancer efficiently, can be administered safely to patients, and has more advantageous pharmacokinetic properties than monoclonal antibodies. Further studies are warranted to determine more accurately the potential of EGF and EGF-related peptides in the imaging and/or therapy of EGFr-overexpressing human cancers.

Aged↗
PubMed1996

Molecular staging of non-small cell lung cancer according to K-ras genotypes.

We have previously demonstrated a strong association between K-ras gene mutations, as determined by PCR followed by allele-specific oligonucleotide hybridization (ASO-h), and survival in non-small cell lung cancer patients. The purpose of this study was to determine the relationship between tumor aggressiveness and specific-type K-ras point mutations in non-small cell lung cancer. We developed procedures to examine the status of the K-ras gene by ASO-h and by single-strand conformation polymorphism assay of DNA obtained from formalin-fixed paraffin-embedded tumors. K-ras point mutations at codons 12 and 61 were assessed in 275 consecutively treated stage I-IV non-small cell lung cancers. Among patients with stage I disease, median survival time was 41.5 months in those whose tumors had no evidence of K-ras mutations and 27 months in those with K-ras 12 mutations; among patients with stage IIIA disease, median survival time was 7 months in those with K-ras codon 12 aspartic and serine mutations and 15 months for those with other K-ras mutations (P = 0.01). In a multivariate analysis, specific-type K-ras codon 12 point mutation remained a strong predictive factor (hazard ratio for death, 2.06; 95% confidence interval, 1.11-3.81; P = 0.02) after adjustment for other evaluated factors, including TNM stage and histology. Thus, we concluded that in patients with non-small cell lung cancer, specific K-ras 12 point mutations detected by DNA amplification and either ASO-h or single-strand conformation polymorphism methods predicted a significantly increased risk of recurrence and death, independently of stage and histology.

Adult↗
PubMed1995

Sequential methotrexate, 5-fluorouracil (5-FU), and high dose leucovorin versus 5-FU and high dose leucovorin versus 5-FU alone for advanced colorectal cancer. A multi-institutional randomized trial.

BACKGROUND: The primary objective of this study was to compare the single-biochemical modulation of 5-fluorouracil (5-FU) and leucovorin with that of the double-biochemical modulation of methotrexate and leucovorin. Because of the Martin et al. study in which an experimental model showed similar effects of 5-FU at maximum tolerated doses to the modulation with leucovorin at standard doses, a third treatment arm of 5-FU alone was also studied. METHODS: A randomized trial was performed using a 500-mg/m2 intravenous (i.v.) 1-hour infusion of methotrexate, and 12 hours later, a 600-mg/m2 i.v. bolus of 5-FU plus a 200-mg/m2 i.v. 1-hour infusion of leucovorin (MFL) every 2 weeks versus 5-FU plus leucovorin at an equal dose and schedule (FL), versus a 1200-mg/m2 i.v. dose of 5-FU every 2 weeks. Of 186 patients included in the study, 178 were evaluable. RESULTS: In a preliminary analysis with 94 evaluable patients, two significant statistical differences were shown. First, the toxicity rate of the 5-FU--alone (F) treatment arm was higher than that of the other arms (MFL vs. F, P = 0.0002; FL vs. F, P = 0.00001). Second, the median survival was worse in the F treatment arm with a rate of 12.6 months for the MFL and FL arms and 7.5 months for the F arm (P < 0.05). Considering these results, the F treatment arm was discontinued. The final results included 70 evaluable patients for MFL and 74 patients for FL. No difference was found in the distribution of prognostic factors. The response rates were 25.7% for MFL (95% CI, 16-37.5) and 14.8% for FL (95% CI, 7.6-25), (P = 0.1). The median survival was 14.3 months for patients treated with MFL and 12.3 months for those treated with FL. The hematologic toxicity was mild, with no grade 3/4 leukopenia in either treatment arm. The major nonhematologic toxicity in the MFL and FL treatment arms was ocular; nongrade 3/4 diarrhea also was observed. CONCLUSIONS: The results of MFL double-biochemical modulation failed to show a significant statistical difference from that of single-biochemical modulation for this dose and schedule.

Adenocarcinoma↗
PubMed1995

Standard and variant CD44 isoforms are commonly expressed in lung cancer of the non-small cell type but not of the small cell type.

Cluster of differentiation 44 (CD44) encompasses a polymorphic family of cell membrane glycoproteins involved in the mechanism of tumour invasion and metastasis. Since non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) display very different rates of progression, a significant discrepancy in their CD44 expression profiles is to be expected. An immunohistochemical study was undertaken on the expression of standard CD44 (CD44s) and the variant isoforms containing the domains encoded by variant exon 3 (CD44v3) or variant exon 6 (CD44v6) in paraffin-embedded bronchial biopsy specimens from 32 NSCLC cases and 11 SCLC cases. An absolute lack of immunoreactivity for CD44s, CD44v3, and CD44v6 was obtained in every case of SCLC, whereas 28 of the 32 NSCLC cases showed a positive immunoreaction for at least one of the three epitopes investigated. In conclusion, the occurrence of standard and variant CD44 isoforms in NSCLC and their absence in SCLC suggest the possibility that CD44 is in some way instrumental in conditioning the biological behaviour of NSCLC, but not of SCLC, whose metastatic cascade would be set in motion by the activation of hitherto unidentified, CD44-independent pathways.

Adult↗