Prognostic value of posttreatment HPV-specific antibodies in patients with oropharyngeal tumors.

BACKGROUND: The presence of human papillomavirus (HPV)-specific antibodies in patients with head and neck cancer at enrollment has prognostic significance. In cervical carcinoma patients, the decrease of HPV E6/E7-specific antibodies appears to be associated with a better prognosis. METHODS: This prospective study with follow-up focused on the persistence and prognostic value of antibodies specific for HR HPV-derived VLPs and HPV16 E6/E7 oncoproteins in patients with oropharyngeal cancers. In this study, we analyzed sera of 93 patients taken a year after the end of treatment and sera from 58 of these patients taken up to 14 years after treatment. RESULTS: The level of HPV-specific antibodies decreased on the 1-year follow-up and the decrease during the long follow-up was statistically significant. For HPV16 E7 antibodies the decrease was steeper in nonrecurrent patients. While the level of antibodies at enrollment was not predictive of recurrences, the decrease of HPV16 E6 antibodies at 1-year follow up was associated with better overall as well as disease-specific survival of patients. CONCLUSIONS: The data suggest that the pretreatment level of HPV-specific antibodies is not predictive of the occurrence of recurrences but the decrease HPV16 E6 antibodies on the 1-year follow-up is predictive of better survival of HN patients.

Plasma selenoprotein P concentration and lung cancer risk: results from a case-control study nested within the Shanghai Men's Health Study.

Selenoprotein P (SELENOP) is a major selenoenzyme in plasma and linked to antioxidant properties and possibly to lung cancer; however, supporting evidence is limited. We investigated the association between pre-diagnostic plasma SELENOP concentration and lung cancer risk in a case-control study of 403 cases and 403 individually matched controls nested within the Shanghai Men's Health Study. SELENOP concentration in pre-diagnostic plasma samples was measured by a sandwich enzyme-linked immunosorbent assay. Cases were diagnosed with lung cancer between 2003 and 2010. Multivariate conditional logistic regression was used to estimate odds ratios (OR) and the corresponding 95% confidence intervals (CI) for studying the association between plasma SELENOP concentration and lung cancer risk. Cases had slightly lower plasma SELENOP concentration than controls (4.3 ± 1.2 versus 4.4 ± 1.1 mg/l, P difference = 0.09). However, the multivariate analysis showed no association between plasma SELENOP concentration and lung cancer risk among all participants (OR = 1.08, 95% CI = 0.54-2.14 for quartile 4 versus quartile 1), or by smoking status or tumor aggressiveness. In contrast, although the number of cases was limited, plasma SELENOP concentration was positively associated with lung adenocarcinoma risk (OR = 5.38, 95% CI = 1.89-15.35 for tertile 3 versus tertile 1), but not with squamous cell lung carcinoma (OR = 1.69, 95% CI = 0.43-6.70). Our study of adult men living in selenium non-deficient areas in China provides little support for the inverse association between pre-diagnostic plasma SELENOP concentration and lung cancer risk. Our finding of a positive association with risk of lung adenocarcinoma needs to be interpreted with caution.

High Expression of S100A6 Predicts Unfavorable Prognosis of Lung Squamous Cell Cancer.

BACKGROUND S100 family of proteins is mainly involved in regulation of intracellular calcium homeostasis. Aberrant expression of S100 family members has been reported in many types of cancers. However, as a member of S100 family, the prognostic value of S100A6 for lung squamous cell carcinoma (SCC) has not been well-studied. MATERIAL AND METHODS Using immunohistochemistry, we investigated the expression of S100A6 in 177 patients with SCC and further divided the cohort into a high S100A6 expression group and a low S100A6 expression group. The chi-square test was applied to analyze the correlation between S100A6 expression and clinicopathological factors. Univariate analysis using the Kaplan-Meier method was performed to compare the difference in survival rates between the high S100A6 expression group and the low S100A6 expression group; multivariate analysis with Cox regression model was used to identify independent prognostic risk factors. RESULTS In our experiment, we demonstrated that the expression of S100A6 was significantly associated with patient age and tumor differentiation. High-expression of S100A6 was shown to be substantially related to the unfavorable prognosis of SCC. Moreover, our results confirmed that S100A6 was an independent risk factor for SCC prognosis, and could predict unfavorable prognosis. CONCLUSIONS High-expression of S100A6 was identified as an independent unfavorable prognostic factor for SCC, suggesting that targeting S100A6 may result in the development of potential targeted drug for SCC.

The blood-borne miRNA signature of lung cancer patients is independent of histology but influenced by metastases.

OBJECTIVES: In our previous studies we reported a panel of 24 miRNAs that allowed discrimination between blood of lung tumor patients independent of the histological subtype and blood of healthy controls with an accuracy of 95.4% [94.9%-95.9%]. Here, we now separately analyzed the miRNA expression in blood of non-small cell lung cancer (NSCLC), including squamous cell lung cancer and adenocarcinoma, and small cell lung cancer (SCLC) patients. PATIENTS AND METHODS: In total, we examined the expression levels of 1,205 miRNAs in blood samples from 20 patients from each of the three histological groups and determined differentially expressed miRNAs between histological subtypes and metastatic and non-metastatic lung cancer. We further determined the overlap of miRNAs expressed in each subgroup with the 24-miRNA signature of lung tumor patients. RESULTS: Based on a raw p-value < 0.05, only 18 blood-borne miRNAs were differentially expressed between patients with adenocarcinoma and with squamous cell lung carcinoma, 11 miRNAs between adenocarcinoma and SCLC, and 2 between squamous cell lung carcinoma and SCLC. Likewise, the comparison based on a fold change of 1.5 did not reveal major differences of the blood-borne miRNA expression pattern between NSCLC and SCLC. In addition, we found a large overlap between the blood-borne miRNAs detected in the three histological subgroups and the previously described 24-miRNA signature that separates lung cancer patients form controls. We identified several miRNAs that allowed differentiating between metastatic and non-metastatic tumors both in blood of patients with adenocarcinoma and in blood of patients with SCLC. CONCLUSION: There is a common miRNA expression pattern in blood of lung cancer patients that does not allow a reliable further subtyping into NSCLC or SCLC, or into adenocarcinoma and squamous cell lung cancer. The previously described 24-miRNA signature for lung cancer appears not primarily dependent on histological subtypes. However, metastatic adenocarcinoma and SCLC can be predicted with 75% accuracy.

Elevated progesterone receptor membrane component 1/sigma-2 receptor levels in lung tumors and plasma from lung cancer patients.

Cancer is one of the leading causes of death, and there is an urgent need for new biomarkers and therapeutic targets. The progesterone receptor membrane component 1 (Pgrmc1) protein is upregulated in multiple types of cancer, and Pgrmc1 is required for tumor cell proliferation, motility and tumor formation in vivo. Furthermore, a small molecule inhibitor of Pgrmc1 suppressed the growth of lung, breast and cervical cancer cell lines. Recently, Pgrmc1 was identified as the sigma-2 receptor, a putative type of opioid receptor, and sigma-2 receptors are induced in cancers. However, Pgrmc1 shares no homology with known opioid or hormone receptors but is related to cytochrome b(5), and Pgrmc1 binds to heme and has reducing activity. In this study, we have analyzed Pgrmc1 levels in clinical tumor samples from squamous cell lung cancers (SCLC) and lung adenocarcinomas compared to corresponding nonmalignant tissue. Pgrmc1 levels increased significantly (p ≤ 0.05) in 12/15 SCLC samples and was elevated in poorly differentiated tumors. Pgrmc1 was highly expressed in SCLC cell lines, and SCLC cell survival was inhibited by siRNA knockdown of Pgrmc1 or the Pgrmc1 inhibitor AG-205. In adenocarcinomas, 6/15 tumors significantly had elevated Pgrmc1 levels, which correlated with patient survival. Pgrmc1 localizes to secretory vesicles in cancer cells, and Pgrmc1 was secreted by lung cancer cells. Furthermore, Pgrmc1 was significantly elevated in the plasma of lung cancer patients compared to noncancer patients. Together, the results demonstrate that Pgrmc1 is a potential tumor and serum biomarker, as well as a therapeutic target, for lung cancer.

Serum midkine as non-invasive biomarker for detection and prognosis of non-small cell lung cancer.

Lung cancer continues to be the leading cause for cancer-related deaths in men and women worldwide. Sufficient screening tools enabling early diagnosis are essential to improve patient outcomes. The aim of this study was to evaluate serum midkine (S-MK) both as a diagnostic and prognostic biomarker in non-small cell lung cancer (NSCLC). This single-center analysis included 59 NSCLC patients counting 30 squamous cell cancers and 29 adenocarcinomas. Preoperative S-MK concentration was determined using ELISA. Patients were followed up to five years. S-MK was found to be significantly overexpressed in patients with NSCLC compared to healthy controls (p < 0.001). The discriminative power of S-MK to differentiate NSCLC subjects from controls was fairly high with an area under the receiver operating characteristic curve of 0.83 (p < 0.001). Optimal sensitivity of 92% and reasonable specificity of 68% was reached at a threshold of 416 pg/ml S-MK. Patients with high S-MK concentration showed a significantly shorter overall survival compared to patients with low S-MK expression (p < 0.05). In conclusion, S-MK is overexpressed in patients with NSCLC and serves as an independent prognostic factor for overall survival. S-MK may thus be considered as an additional non-invasive biomarker not only for NSCLC screening but also for outcome prediction.

[Diagnostic and prognostic biomarkers in head and neck squamous cell carcinoma]. / Tumormarker und Prognosefaktoren bei Plattenepithelkarzinomen der Kopf-Hals-Region.

Classical prognostic factors for squamous cell carcinoma of the head and neck (HNSCC) are based on general parameters such as tumor stage or histological grading and only allow for a rough estimation of the clinical course. However, predicting individual responses to treatment remains challenging and diverging clinical courses of same-stage HNSCC stage remain obscure. The need for a better understanding of the individual genomic or proteomic signature of HNSCC resulted in a great number of publications on novel biomarkers. Still, in most cancer centres therapy planning and risk appraisal are solely based on the classical factors with only a few exceptions such as HPV status in oropharyngeal carcinoma. Future improvements in biomarker research will probably be achieved with sets of various genomic and proteomic markers as provided by microarray technology. This review highlights the criteria for a successful biomarker candidate, gives an overview on the most important new biomarkers, and introduces the principles of genomic and proteomic biomarker chips.

Is smoking an independent risk factor for invasive cervical cancer? A nested case-control study within Nordic biobanks.

The strong correlation between smoking and exposure to oncogenic human papillomaviruses (HPVs) has made it difficult to verify the independent role of smoking in cervical carcinogenesis. Thus, the authors evaluated this role. Five large Nordic serum banks containing samples from more than 1,000,000 subjects were linked with nationwide cancer registries (1973-2003). Serum samples were retrieved from 588 women who developed invasive cervical cancer and 2,861 matched controls. The samples were analyzed for cotinine (a biomarker of tobacco exposure) and antibodies to HPV types 16 and 18, herpes simplex virus type 2, and Chlamydia trachomatis. Smoking was associated with the risk of squamous cell carcinoma (SCC) among HPV16- and/or HPV18-seropositive heavy smokers (odds ratio=2.7, 95% confidence interval: 1.7, 4.3). A similar risk of SCC (odds ratio=3.2, 95% confidence interval: 2.6, 4.0) was found in heavy smokers after adjustment for HPV16/18 antibodies. The point estimates increased with increasing age at diagnosis and increasing cotinine level. This study confirms that smoking is an independent risk factor for cervical cancer/SCC in women infected with oncogenic HPVs. These findings emphasize the importance of cervical cancer prevention among women exposed to tobacco smoke.

Less circulating mucosal-associated invariant T cells in patients with cervical cancer.

OBJECTIVE: Mucosal-associated invariant T cells (MAITs) are important for immune defense against infectious pathogens and regulation of various inflammatory diseases. However, their roles in cancer are rarely reported. Since cervical cancer is one of the diseases involving mucosal tissue, we try to investigate the association between circulating MAITs and cervical cancer. MATERIALS AND METHODS: Blood samples were obtained from patients with cervical cancer (n = 47) and healthy individuals (n = 39). We determined phenotypic MAITs in peripheral blood mononuclear cells (PBMCs) and evaluated the percentage of MAITs in CD3+ cells by flow cytometry. The percentage of MAITs was stratified according to Federation of Gynecology and Obstetrics (FIGO) staging system in patients with cervical cancer. Progression-free survival (PFS) with respect to the amount of MAITs was also analyzed. RESULTS: The percentage of circulating MAITs in patients with cervical cancer was significantly lower than in healthy group (0.987% vs. 4.008%, p < 0.0001). In subgroup analysis, though not statistically significant, it showed a trend of lower percentage of circulating MAITs in cervical cancer patients with FIGO stage II-IV disease than in patients with FIGO stage I disease (0.4045% vs. 1.098%, p = 0.11). A trend of poor PFS in patients with lower circulating MAITs was also noted. CONCLUSION: MAITs play a crucial role in cancer immunity. The decrease of MAITs in peripheral blood is related to cervical cancer. There is a trend of lower percentage of MAITs in advanced stages and lower percentage of MAITs towards poor PFS in patients with cervical cancer.

Differentially expressed serum haptoglobin alpha chain isoforms with potential application for diagnosis of head and neck cancer.

BACKGROUND: The discovery of molecular biomarkers is crucial to the diagnosis of head and neck squamous cell cancer (HNSCC). METHODS: Proteins from pre-surgery serum samples of patients with HNSCC and healthy individuals were analyzed by 2-dimensional gel electrophoresis (2-DE) using a 17 cm-long immobilized pH gradient gel strip (large gel). The differentially expressed protein spots were detected by statistical analysis. Because 2 haptoglobin (Hp) alpha chains were found to be differentially expressed, the genotypic distribution of Hp alpha chains in patients and healthy individuals was assayed by polymerase chain reaction. The protein expression levels of Hp alpha chains in individuals carrying different Hp alleles were analyzed by 2-DE with a small gel. RESULTS: Two isoforms of haptoglobin alpha2 chain (Hp alpha2) in patients' sera were found from 2-DE analysis to be up-regulated, while the isoforms of haptoglobin alpha1 chain (Hp alpha1) were significantly down-regulated. Apolipoprotein AII and 2 isoforms of apolipoprotein CII were also differentially expressed in the sera of patients with HNSCC. The Hp alpha2 chain was significantly up-regulated in the patients carrying at least one haptoglobin 2 allele, according to the spot intensities from scanned images of small-gel 2-DE. CONCLUSIONS: The expression pattern of seven differentially expressed polypeptides and the up-regulation of Hp alpha2 in individuals with the Hp 2 allele are potential biomarkers.

[Impact of squamous cell carcinoma antigen in patients with recurrent squamous cell carcinoma of the uterine cervix].

OBJECTIVE: To investigate the impact of squamous cell carcinoma antigen (SCCAg) in patients with recurrent squamous cell carcinoma of the uterine cervix. METHODS: Totally 72 patients with recurrent squamous cell carcinoma of the uterine cervix treated at the Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, between 1999 and 2005 were retrospectively analyzed to investigate the impact of SCCAg on diagnosis and prognosis by univariate and multivariate analysis. RESULTS: This study included 30 patients with recurrent disease after primary radical surgery and 42 patients with recurrent cervical cancer after radio-chemotherapy. Sixty one patients (85%) had serum SCCAg elevated (>or=1.5 pg/L), and 20 of these (28%) had an increase of SCCAg before clinical manifestation of relapse. The median leading time was 3 months (range: 1-13 months). Forty five patients had no symptoms with only SCCAg elevation, and 15 patients experienced leg edema and (or) sciatic pain, 7 patients suffered from irregular bleeding and 5 patients had symptoms resulting from distant metastasis. Thirty three patients were diagnosed by histology biopsy and (or) cytology, 39 patients were diagnosed with SCCAg elevation and clinical and radiological examinations, 29 of these patients were diagnosed only by SCCAg elevation and CT or MRI. Fourteen patients recurred limited to the cervix or to the cervix and adjacent tissues (central recurrence), 31 cases recurred at pelvis, and 20 patients with distant metastasis and 7 patients suffered from pelvic recurrence and distant metastasis. Twenty three cases received salvage therapy including surgery for patients recurring after definitive radiotherapy and radiotherapy and or conform radiotherapy for patients after primary radical surgery, 46 patients were given palliative chemotherapy and or radiotherapy, and 3 patients refused any treatment. The median and mean survival time were 11 months and 23 months respectively (2-62 months). The 3-year, 5-year overall survival rate were 25% and 19% respectively. Univariate analysis showed SCCAg elevation before primary treatment, grade, recurrent site, treatment method, SCCAg>or=10 pg/L, SCCAg elevation during treatment, and SCCAg not within normal after treatment were correlated with 3-year survival rate. Twenty patients had an increase of SCCAg before clinical manifestation of relapse compared with other patients who did not, and the 3-year survival rate was not significantly different (22% vs 27%). Multivariate analysis revealed that only grade and treatment methods were independent risk factors. CONCLUSION: The impact of the SCCAg in recurrent squamous cell carcinoma of the uterine cervix needs further study.

Circulating Heat Shock Protein 70 Is a Novel Biomarker for Early Diagnosis of Lung Cancer.

Heat shock protein 70 (HSP70) was a highly conserved protein which was significantly induced in response to cellular stresses. HSP70 played an important role in the pathogenesis of cancer which stabilized the production of large amount of oncogenic proteins and finally supported growth and survival of tumor. However, there was no report about the diagnosis of circulating HSP70 in lung cancer patients. In this study, a total of 297 participants (lung cancer: 197, healthy control: 100) were enrolled in the detection of circulating HSP70 level in plasma by ELISA assay. The results indicated that circulating HSP70 significantly decreased in lung cancer patients compared to healthy controls (P < 0.0001). Receiver operating characteristic (ROC) analysis showed that HSP70 (AUC: 82.2%, SN: 74.1%, SP: 80.0%) had higher diagnosis value than clinical existing biomarkers CEA (AUC: 80.1%, SN: 76.8%, SP: 67.3%) and CA 19-9 (AUC: 63.7%, SN: 64.2%, SP: 54.0%). In the analysis of early lung cancer patients, ROC results also revealed that HSP70 (AUC: 83.8%, SN: 71.2%, SP: 84.0%) have higher sensitivity, specificity, and AUC than CEA (AUC: 73.7%, SN: 73.2%, SP: 69.1%) and CA 19-9 (AUC: 61.5%, SN: 69.4%, SP: 53.4%). In analysis of specific histological classifications, HSP70 showed more valuable in the diagnosis of SCC (AUC: 85.9%, SN: 86.1.9%, SP: 81.0%) than ADC (AUC: 81.0%, SN: 69.1%, SP: 81.0%). Combined analysis of HSP70 and existing biomarker: CEA and CA 19-9 exhibited that HSP70 combined CEA and CA 19-9 showed the highest AUC (0.945, 95% CI, 0.855-1.000). The importance of our results was that we found decreased circulating HSP70, in combination with elevated CEA and CA 19-9, could be utilized in the diagnosis of early (stage I and II) lung cancer.

Levels of fat-soluble micronutrients and 2,6-cyclolycopene-1,5-diol in head and neck cancer patients.

Smoking negatively affects serum carotenoid levels, and it is a negative prognostic factor for head and neck cancer. In this study, micronutrient levels were examined in 60 smoking and non-smoking head and neck cancer patients. The goal was to determine if oxidation of the carotenoid lycopene would occur to a greater extent in smokers. Subjects were drawn from a prospective cohort study and matched on seven demographic factors. Serum levels of alpha-carotene, zeaxanthin, and 2,6-cyclolycopene-1,5-diol A, an oxidation product of lycopene, were all lower in smokers versus non-smokers (18%, 22%, and 8%, respectively) while beta-carotene, beta-cryptoxanthin, and lutein were about the same in the two groups. Levels of lycopene, gamma-tocopherol, and alpha-tocopherol were higher in smokers, and notably serum alpha-tocopherol was 48% higher in smokers. The majority of vitamin E intake was from supplements. The higher levels of alpha-tocopherol in smokers were interesting in that higher alpha-tocopherol levels have been associated with higher mortality in head and neck cancer. Although this was a pilot investigation, there was no evidence that 2,6-cyclolycopene-1,5-diol A formation was appreciably affected by smoking status, but alpha-tocopherol levels were higher in smokers.

[Correlation of serum squamous cell carcinoma antigen with clinico-pathological features and prognosis of squamous cell carcinoma of uterine cervix].

OBJECTIVE: To investigate the correlation of pretreatment serum squamous cell carcinoma antigen (SCCAg) with the clinico-pathological features of squamous cell carcinoma of uterine cervix and its significance as a prognostic factor. METHODS: One hundred and fourteen patients of squamous cell carcinoma of the uterine cervix (Ib1-IIa), who underwent pretreatment serum SCCAg evaluation and long-term follow-up after treatment were selected for this study. Clinical data were used to investigate the correlation between SCCAg and clinico-pathological features and factors that influence prognosis through univariate and multivariate analysis. RESULTS: Univariate analysis showed elevation of SCCAg (using < or = 1.5 mg/L as the cut-off value) was correlated with tumor size, deep stromal invasion and pelvic node metastasis (P < 0.05). Multivariate analysis revealed significant correlations between elevation of SCCAg and deep stromal invasion (P = 0.029) and pelvic node metastasis (P = 0.049). The 5 years disease-free survival (DFS) was 78.6%, and recurrence rate was 27.2%. Univariate analysis revealed that elevated pretreatment SCCAg and pelvic node metastasis were significantly correlated with DFS and recurrence (P < 0.05). Multivariate analysis identified elevated pretreatment SCCAg (P = 0.030), pelvic node metastasis (P = 0.003) as independent prognostic factors, and pelvic node metastasis (P = 0.006) as a factor significantly correlated with recurrence after treatment. Comparison between pelvic node metastasis + elevated SCCAg cases and pelvic node metastasis + normal SCCAg cases showed no significant difference in DFS (50.9% vs 50.0%), recurrence rate (47.1% vs 60.0%), local recurrence (20.0% vs 3/8) and distant recurrence (20.0% vs 1/8; all P > 0.05). However, between no pelvic node metastasis + elevated SCCAg cases and no pelvic node metastasis + normal SCCAg cases, there was a significant difference in DFS (71.8% vs 98.0%, P = 0.003), recurrence rate (33.3% vs 9.8%, P = 0.006) and local recurrence (26.5% vs 2.1%, P = 0.001). CONCLUSIONS: The independent prognostic factors for Ib1-IIa squamous cell carcinoma of uterine cervix include elevated pretreatment SCCAg and pelvic node metastasis. Patients with elevated pretreatment serum SCCAg and no metastasis to pelvic lymph node (s) are at significantly elevated risk of local recurrence, and therefore need individualized treatment to improve local control and long-term survival.

Inhibition of squamous cancer growth in a mouse model by Staphylococcal enterotoxin B-triggered Th9 cell expansion.

Currently, therapy for squamous cancer (SqC) is unsatisfactory. Staphylococcal enterotoxin B (SEB) has strong immune regulatory activity. This study tests the hypothesis that SEB enforces the effect of immunotherapy on SqC growth in a mouse model. C3H/HeN mice and the SqC cell line squamous cell carcinoma VII were used to create an SqC mouse model. Immune cell assessment was performed by flow cytometry. Real-time RT-PCR and western blotting were used to evaluate target molecule expression. An apoptosis assay was used to assess the suppressive effect of T helper-9 (Th9) cells on the SqC cells. The results showed that immunotherapy consisting of SEB plus SqC antigen significantly inhibited SqC growth in the mice. The frequency of Th9 cells was markedly increased in the SqC tissue and mouse spleens after treatment. SEB markedly increased the levels of signal transducer and activator of transcription 5 phosphorylation and the expression of histone deacetylase-1 (HDAC1) and PU.1 (the transcription factor of the interleukin 9 (IL-9) gene) in CD4+ T cells. Exposure to SqC-specific Th9 cells markedly induced SqC cell apoptosis both in vitro and in vivo. In conclusion, the administration of SEB induces Th9 cells in SqC-bearing mice, and theseTh9 cells inhibit SqC growth.

Detection and staging of preinvasive lesions and occult lung cancer in the central airways with 18F-fluorodeoxyglucose positron emission tomography: a pilot study.

PURPOSE: To evaluate the role of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in radiologically occult preinvasive lesions and lung cancer in the central airways. EXPERIMENTAL DESIGN: Twenty-two patients with 24 preinvasive lesions and early squamous cell cancer (SCC) being occult on high-resolution computed tomography were studied. All lesions were diagnosed based on histology sampled using autofluorescence bronchoscopy. FDG-PET findings were correlated with WHO histologic classification. FDG-PET was considered true-positive when the final diagnosis was SCC and true-negative when the lesions were classified as severe dysplasia or less. RESULTS: FDG-PET was true-positive in 8 of 11 and true-negative in 11 of 13 cases corresponding with a sensitivity of 73% [95% confidence interval (CI), 0.43-0.91] and specificity of 85% (95% CI, 0.57-0.97). Positive and negative predictive values were 80% (95% CI, 0.48-0.96) and 79% (95% CI, 0.52-0.93), respectively. CONCLUSIONS: Our very preliminary data suggest that FDG-PET might be useful for the evaluation of early central airway lesions, being positive in most SCC and negative in cases of severe dysplasia. Validation in a larger multicenter study is needed.

Serum levels of insulin-like growth factor-I and -II and insulin-like growth factor binding protein 3 in women with squamous intraepithelial lesions and cervical cancer.

INTRODUCTION: Pap smear has limitations as a screening test for cervical cancer. A marker that allows the identification of women who are at risk of developing cervical cancer would be useful for its prevention. A growing number of studies have demonstrated an association between insulin-like growth factors (IGF) serum levels and increased risk for various cancers. Objective. To assess whether circulating IGF-I, IGF-II, or IGF binding protein 3 (IGFBP-3) were associated with cervical cancer and low-grade and high-grade squamous intraepithelial lesions (LSIL and HSIL). MATERIALS AND METHODS: Serum levels of IGF-I, IGF-II and IGFBP-3 were measured by ELISA. Three groups of cases were analyzed: LSIL (n = 37), HSIL (n = 57), and cervical cancer (n = 41). For each case, two controls, matched by age, were included. Control subjects were women with normal, HPV-DNA-negative Pap smear. RESULTS: Significantly lower values of IGF-I (83.9 ng/ml versus 126.6 ng/ml, p < 0.001) and IGF-I:IGFBP-3 molar ratio (0.094 versus 0.137, p < 0.001) were observed among cancer cases, as compared to their control group. Women in the highest quartile of IGF-I and IGF-I:IGFBP-3 molar ratio were at an 80% (OR = 0.2, 95% CI [0.06-0.61]) and a 77% (OR = 0.23, 95% CI [0.07-0.73]) lower risk of cervical cancer, respectively, compared with women in the corresponding reference category. CONCLUSIONS: These data suggest that low values of IGF-I and IGF-I:IGFBP-3 molar ratio may be associated with cervical cancer.

The use of plasma surface-enhanced laser desorption/ionization time-of-flight mass spectrometry proteomic patterns for detection of head and neck squamous cell cancers.

PURPOSE: Our study was undertaken to determine the utility of plasma proteomic profiling using surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry for the detection of head and neck squamous cell carcinomas (HNSCCs). EXPERIMENTAL DESIGN: Pretreatment plasma samples from HNSCC patients or controls without known neoplastic disease were analyzed on the Protein Biology System IIc SELDI-TOF mass spectrometer (Ciphergen Biosystems, Fremont, CA). Proteomic spectra of mass:charge ratio (m/z) were generated by the application of plasma to immobilized metal-affinity-capture (IMAC) ProteinChip arrays activated with copper. A total of 37356 data points were generated for each sample. A training set of spectra from 56 cancer patients and 52 controls were applied to the "Lasso" technique to identify protein profiles that can distinguish cancer from noncancer, and cross-validation was used to determine test errors in this training set. The discovery pattern was then used to classify a separate masked test set of 57 cancer and 52 controls. In total, we analyzed the proteomic spectra of 113 cancer patients and 104 controls. RESULTS: The Lasso approach identified 65 significant data points for the discrimination of normal from cancer profiles. The discriminatory pattern correctly identified 39 of 57 HNSCC patients and 40 of 52 noncancer controls in the masked test set. These results yielded a sensitivity of 68% and specificity of 73%. Subgroup analyses in the test set of four different demographic factors (age, gender, and cigarette and alcohol use) that can potentially confound the interpretation of the results suggest that this model tended to overpredict cancer in control smokers. CONCLUSIONS: Plasma proteomic profiling with SELDI-TOF mass spectrometry provides moderate sensitivity and specificity in discriminating HNSCC. Further improvement and validation of this approach is needed to determine its usefulness in screening for this disease.

Post-treatment plasma transforming growth factor beta 1 (TGF-beta1) level predicts for late morbidity in patients with advanced head and neck cancer.

Between 2001 and 2002, 29 patients with advanced inoperable squamous head and neck cancer treated with radiotherapy with or without simultaneous chemotherapy were evaluated for their plasma TGF-beta1 levels prior to the treatment, in the middle of the radiotherapy course and at the end of the treatment. Patients were assessed for treatment response and late morbidity. Predictive value of TGF-beta1 level on either of the assessed parameters was tested. From 29 eligible patients (pts), 18 achieved complete response, 8 partial response and three pts progressed primarily. After a median follow-up of 16 months we recorded 16 cases of grade >1 late morbidity. We found that post-treatment elevated plasma TGF-beta1 level predicts late morbidity grade >1 (p=0.05) rather than pre-treatment level (p=0.062). Neither pre-treatment nor post-treatment plasma TGF-beta1 level has a predictive value to the treatment response (CR vs. no CR, p=0.125 and 0.252, respectively). The post-treatment plasma TGF-beta 1 level can predict late morbidity grade >1 in advanced head and neck cancer treated with radio(chemo)therapy. This could make a basis for dose escalation in selected patients.

Vascular endothelial growth factor (VEGF-A) plasma levels in non-small cell lung cancer: relationship with coagulation and platelet activation markers.

Platelet activation, commonly found in lung cancer patients, may cause the release of angiogenic factors, such as vascular endothelial growth factor (VEGF-A). The present study was designed to investigate whether plasma VEGF-A levels were associated to different stages of non-small cell lung cancer (NSCLC). Moreover, sP-selectin, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin III complex (TATc) and D-dimer levels were measured to test the hypothesis of an involvement of platelet and coagulation activation in tumor angiogenesis. VEGF-A, sP-selectin, F1+2, TATc and D-dimer levels were elevated in 65 patients with NSCLC, particularly in metastatic patients. sP-selectin (p <0.003) and F1+2 (p <0.005) levels were independently associated to VEGF-A. In addition, patients with positive levels of both sP-selectin and F1+2 had the highest levels of VEGF-A. In conclusion, our findings support the hypothesis that thrombin generation might induce platelet activation and VEGF-A release in NSCLC.