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Background: To compare adenocarcinoma (AC) and adenosquamous carcinoma (ASC) prognoses in patients with FIGO stage IB-IIA cervical cancer who underwent radical hysterectomy., Methods: We performed a retrospective analysis of 240 patients with AC and 130 patients with ASC. Kaplan-Meier curves, Cox regression models, and log-rank tests were used for statistical analysis., Results: Patients with ASC had higher frequencies of lymphovascular space invasion (LVSI) and serum squamous cell carcinoma antigen (SCC-Ag) > 5 ng/ml (p = 0.049 and p = 0.013, respectively); moreover, they were much older (P = 0.029) than patients with AC. There were no clinically significant differences in overall survival (OS) between the groups. When stratified into three risk groups based on clinicopathological features, survival outcomes did not differ between patients with AC and those with ASC in any risk group. Multivariate analysis showed that lymph node metastasis (LNM) was an independent risk factor for recurrence-free survival (RFS) and OS in patients with AC and in patients with ASC. Carcinoembryonic antigen (CEA) > 5 ng/ml and SCC-Ag > 5 ng/ml were independent predictors of RFS and OS in patients with AC. In addition, among those stratified as intermediate-risk, patients with ASC who received concurrent chemoradiotherapy (CCRT) had significantly better RFS and OS (P = 0.036 and P = 0.047, respectively)., Conclusions: We did not find evidence to suggest that AC and ASC subtypes of cervical cancer were associated with different survival outcomes. CCRT is beneficial for survival in intermediate-risk patients with ASC, but not in those with AC. Serum tumour markers can assist in evaluating prognosis and in providing additional information for patient-tailored therapy for cervical AC.

PURPOSE : Circulating tumour DNA (ctDNA) is a promising biomarker for detection of non-invasive epidermal growth factor receptor ( EGFR ) mutations in patients with non-small-cell lung cancer (NSCLC). However, the existing methods have limitations in sensitivity or in availability. The aim was to evaluate the accuracy of capture target sequencing for detecting EGFR mutations in ctDNA. METHODS : A total of 79 patients with NSCLC and available plasma and matched tissue specimens were enrolled. Through capture target sequencing, mutations were searched in over 20 000 reads obtained from each exon region. Parameters corresponding to the limit of detection and limit of quantification were used as the thresholds for mutation detection. To evaluate the accuracy, detection of EGFR mutations in matched tissue samples was performed by target capture sequencing and the amplification refractory mutation system (ARMS). RESULTS:   : EGFR mutations were discovered in 32.9 % (26/79) of the patients with NSCLC, the overall rate of consistency for the 79 paired plasma and tissue samples was 86.1 % (68/79). The sensitivity and specificity of detecting EGFR mutations in the plasma were 72.7 % and 95.7 %. In terms of the EGFR mutations identified by ARMS, the overall consistency was 78.5 % (62/79) in three groups. Of 21 patients with EGFR sensitive mutation defined by next generation sequencing in ctDNA, 20 (95.2%) showed long-term disease control with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) treatment; the median progression-free survival was 10.8 months (95% CI 9.1 to 16.8). CONCLUSIONS: Target capture sequencing of ctDNA can be used for genotyping of EGFR in patients with NSCLC, which may enable a direct recommendation for EGFR TKI on the basis of positive results with plasma DNA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (Copyright © 2018. Published by Elsevier B.V.)

Arctigenin is evaluated for antitumor efficacy in patients with pancreatic cancer. It has an inhibitory activity on mitochondrial complex I.Therefore, plasma lactate level of patients after arctigenin administration was evaluated for biomarker of clinical response and/or adverse effect. Plasma lactate level in 15 patients enrolled in a Phase I clinical trial of GBS-01 rich in arctigenin was analyzed by colorimetric assay. Statistical analyses for association of plasma lactate and clinical responses, pharmacokinetics of arctigenin, and background factors of each patient by multivariate and univariate analyses.In about half of the patients, transient increase of lactate was observed. Correlation between plasma lactate level and pharmacokinetic parameters of arctigenin and its glucuronide conjugate, and clinical outcome was not detected. Regarding to the determinant of lactate level, only slight association with liver function test was detected. Plasma lactate level is primary determined by reutilization rather than production for antitumor effect and dose not serve as a biomarker. Arctigenin, inhibition of mitochondrial complex I, plasma lactate concentration, phase I clinical trial of GBS-01, Cori cycle., Competing Interests: S. Kishino have received the commissioned research funding from Kracie Pharmaceutical Company within one year. S.Y. is an employee of Kracie Pharmaceutical Company. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors declare no conflict of interest.

This study aimed to evaluate the prognostic value of ABO blood groups in early-stage cervical cancer patients. The cohort included 413 patients diagnosed with stages IA2-IB1 cervical cancer who received a radical hysterectomy between 2002 and 2014. The 5-year recurrence-free survival (RFS) and overall survival (OS) were 93.13 and 96.81 % for blood group O, 87.68 and 88.22 % for blood group A, 81.66 and 89.40 % for blood group B, and 83.12 and 94.12 % for blood group AB groups, respectively. Patients were stratified for analysis as either blood group O or non-O. The 5-year RFS and OS were 93.13 and 96.81 % for blood group O and 83.66 and 89.76 % for blood group non-O, respectively. In multivariate analysis, age (P = 0.025), histology (P = 0.020), and deep stromal invasion (P = 0.006) were independent adverse prognostic factors for RFS, while the statistically significant independent prognostic factors for OS were age (P = 0.007) and parametrial involvement (P < 0.001). The Cox model did not show any significant effects of non-O blood group on survival outcome. However, a time-varying-effect Cox model revealed that the non-O blood group was associated with a worse RFS (hazard ratio (HR) 2.69, 95 % confidence interval (95%CI) 1.12-6.46, P = 0.017) and OS (HR 3.13, 95%CI 0.88-11.16, P = 0.053) during the first 5 years. These findings suggest that early-stage cervical cancer patients with a non-O blood group have poorer RFS than the O blood group, which is evidence during the first 5 years.

Objectives: Primary adenosquamous carcinoma (ASC) of the lung is rare. The current study was a retrospective two-institutional analysis of surgical therapy with respect to the clinicopathological characteristics and prognostic factors associated with ASC of the lung., Methods: The clinical records of patients with pathologically confirmed ASC of the lung treated surgically in two centres between January 2008 and December 2014 were retrospectively reviewed., Results: One hundred and four patients with ASC of the lung after surgical intervention, including 68 males and 36 females were identified. The 5-year overall survival (OS) and disease-free survival (DFS) of all ASC stages were 38.3 and 16.9%, respectively. Patients with N0, N1 and N2 ASC [N0 vs N1 (P = 0.047) and N1 vs N2 (P = 0.028), respectively], or Stage I, II and IIIA ASC [Stage I vs Stage II (P = 0.005) and Stage II vs Stage IIIA (P = 0.016), respectively] had significant differences with respect to OS. Multivariate analysis using a Cox proportional hazards model indicated that the level of serum carbohydrate antigen 12-5 (CA 12-5) (normal vs high level, P = 0.029), TNM stage [Stage I vs Stage IIIA (P < 0.001), Stage II vs Stage IIIA (P = 0.001)] and adjuvant chemotherapy (P = 0.027) were significant factors associated with OS in ASC patients, and TNM stage [Stage I vs Stage IIIA (P < 0.001), Stage II vs Stage IIIA (P = 0.003)] and adjuvant chemotherapy (P < 0.001) were the significant prognostic variables for DFS., Conclusions: Serum CA 12-5 level and TNM status predict the long-term prognosis of resected primary ASC of the lung. Postoperative platinum-based chemotherapy improved survival in patients with ASC., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

We hypothesized that plasma-based EGFR mutation analysis for NSCLC may be feasible for monitoring treatment response to EGFR TKIs and also predict drug resistance.Clinically relevant mutations including exon 19 deletion (ex19del), L858R and T790M were analyzed using droplet digital PCR (ddPCR) in longitudinally collected plasma samples (n = 367) from 81 NSCLC patients treated with EGFR TKI. Of a total 58 baseline cell-free DNA (cfDNA) samples available for ddPCR analysis, 43 (74.1%) had the same mutation in the matched tumors (clinical sensitivity: 70.8% [17/24] for L858R and 76.5% [26/34] for ex19del). The concordance rates of plasma with tissue-based results of EGFR mutations were 87.9% for L858R and 86.2% for ex19del. All 40 patients who were detected EGFR mutations at baseline showed a dramatic decrease of mutant copies (>50%) in plasma during the first two months after treatment. Median progression-free survival (PFS) was 10.1 months for patients with undetectable EGFR v 6.3 months for detectable EGFR mutations in blood after two-month treatment (HR 3.88, 95% CI 1.48-10.19, P = 0.006). We observed emerging resistance with early detection of T790M as a secondary mutation in 14 (28.6%) of 49 patients. Plasma-based EGFR mutation analysis using ddPCR can monitor treatment response to EGFR TKIs and can lead to early detection of EGFR TKIs resistance. Further studies confirming clinical implications of EGFR mutation in plasma are warranted to guide optimal therapeutic strategies upon knowledge of treatment response and resistance.

Objective: To evaluate the impact of comorbid diabetes mellitus (DM) on prognoses among patients with cervical cancer., Methods: We analyzed cervical cancer outcomes in patients who treated in two hospitals retrospectively. Patients were divided into those with DM and those without. Clinicopathologic parameters, disease-free survival (DFS), and overall survival (OS) rates were evaluated., Results: Of the 494 patients, 50 had DM. These were more likely to be older than those in the non-DM group and their body mass index (BMI) was higher. They showed higher levels of tumor markers and had more combined diseases. They were less likely to have had surgical treatment. Among these patients, 12 (24%) experienced a recurrence (hazard ratio, HR, 1.484; 95% confidence interval, CI, 0.746-2.951). Differences in DFS did not show statistical significance. In the OS analysis, 11 (22%) in the DM group and 62 (14%) in the non-DM group died (HR, 1.239; 95% CI, 0.606-2.533). No statistically significant differences were also observed for cancer-specific death (HR, 1.246; 95% CI, 0.567-2.737). Those with DM and an adenocarcinoma tended to have an increased risk of dying compared with the non-DM patients with an adenocarcinoma (HR, 3.673; 95% CI, 0.990-13.625), but this difference was not statistically significant (p=0.0518)., Conclusion: Diabetes mellitus did not have an impact on the prognosis for patients with cervical cancers. In those with an adenocarcinoma, patients with diabetes tended to have an increased risk of dying compared with the non-DM group, but this difference was not statistically significant., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) were immune response-related indicators. Preoperative NLR and PLR had been considered to be related to the prognosis of various cancers. The objective of this study was to evaluate the prognostic significance of NLR and PLR in patients with gallbladder carcinoma (GBC)., Methods: From 2001 to 2013, 145 patients with GBC were recruited in this retrospective study. Cutoff values of NLR and PLR were determined by receiver operating characteristic curves (ROC). The correlation of clinical data, including tumor differentiation, nevin stage, TNM stage, operation margin, operation mode, NLR, PLR, hemoglobin, C reactive protein (CRP), carcinoembryonic antigen (CEA), and carbohydrate antigen 199 (CA199) with median survival period of patients was analyzed by univariate survival analysis. The multivariate prognosis analysis was performed to select the independent prognostic factors., Results: The cutoff values of NLR and PLR were 1.94 and 113.34, respectively. Compared with low NLR and low PLR group, the 5-year survival rates in high NLR and high PLR group were reduced (P < 0.05). The degree of tumor differentiation, nevin stage, TNM stage, operation mode, NLR, PLR, CA199, total bilirubin, CRP and CEA were associated with the median survival period of patients (P < 0.01). The multivariate prognosis analysis showed that NLR, nevin stage, operation mode and hemoglobin were independent prognostic factors (P < 0.05)., Conclusion: Preoperative NLR and PLR were closely related to prognosis of patients with GBC and might be useful for the evaluation of prognosis of patients with GBC.

Downregulation of major histocompatibility complex class I chain-related molecule A (MICA) and upregulation of human leukocyte antigen G (HLA-G) on the tumor cells are important immune escape mechanisms for different epithelial tumors. In addition, upregulation of the soluble forms of the latter molecules in serum leads to peripheral T-cell and natural killer (NK)-cell tolerance. As for cervical cancer, it remains unknown whether soluble MICA (sMICA) and soluble HLA-G (sHLA-G) concentrations are related to tumor characteristics or patient survival rates. We measured sMICA and sHLA-G in pre-treatment sera of a large cohort of cervical cancer patients (n = 366) by enzyme-linked immunosorbent assay (ELISA). We detected a median sMICA of 174.73 pg/ml and a median sHLA-G of 5.35 U/ml. We did not find an association between sHLA-G levels and clinicopathological characteristics. In adenocarcinoma, low sMICA concentration was positively related to recurrent disease, a higher International Federation of Gynecology and Obstetrics (FIGO) stage and vaginal involvement (Mann-Whitney U-test; P = 0.018, P = 0.042 and P = 0.013, respectively). In the latter patient group, high sMICA levels were associated with better disease-free survival (DFS) and disease-specific survival (DSS) (P = 0.011 and P = 0.047). After adjusting for confounding factors, high sMICA proved to be an independent predictor for a better DFS and DSS [HR 0.16; 95% confidence interval (CI) 0.04-0.64; P = 0.009 and HR 0.12; 95% CI 0.03-0.50; P = 0.004]. sHLA-G did not influence survival in cervical cancer patients, regardless of histology. We conclude that cervical adenocarcinoma patients with high sMICA levels have an increased DFS and DSS. This data warrants a prospective trial to study the functional role of sMICA in cervical adenocarcinoma., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Several prognostic factors have been studied in NSCLC, although it is unknown which is most useful. In this study, we aimed to investigate whether pre-treatment serum albumin level has prognostic value in patients with Stage IIIB NSCLC., Materials and Methods: This cross-sectional study included a total of 204 patients with Stage IIIB NSCLC who met the inclusion criteria. Pre-treatment serum albumin levels and demographic, clinical, and histological characteristics, as well as laboratory variables were recorded. A cut-off value was defined for serum albumin level and the patients were stratified into four groups on thios basis., Results: The majority of the patients was males and smokers, with a history of weight loss, and squamous histological type of lung cancer. The mean serum albumin level was 3.2±1.7 g/dL (range, 2.11-4.36 g/dL). A cut-off value 3.11 g/dL was set and among the patients with a lower level, 68% had adenocarcinoma and 82% were smokers. The patients with low serum albumin levels had a lower response rate to e first-line chemotherapy with a shorter progression-free survival and overall survival. Multivariate analysis showed that low serum albumin level was an independent poor prognostic factor for NSCLC., Conclusions: This study results suggest that low serum albumin level is an independent poor prognostic factor in patients with Stage IIIB NSCLC, associated with reduction in the response rate to first-line therapy and survival rates.

Background: We evaluated the prognostic value of pretreatment serum biomarkers in predicting outcomes in cervical cancer patients subjected to treatment., Methods: Serum samples collected from 60 cervical cancer patients and 60 age-matched healthy individuals were used for the detection of 22 biomarkers, prior to therapy. Cox multivariate analysis and classification and regression tree analysis (CART) were performed to evaluate the prognostic factors., Results: Cox multivariate analysis disclosed that carbohydrate antigen 153 (CA153), squamous cell carcinoma antigen (SCC) and tumor necrosis factor-α (TNF-α) are associated with prognosis in cervical cancer. CART analysis led to the stratification of patients into 3 groups: (1) serum concentrations of CA153 ≥17.60 μg/l, (2) serum concentrations of CA153 <17.60 μg/l and TNF-α ≥10.60 pg/ml, and (3) serum concentrations of CA153 <17.60 μg/l and TNF-α <10.60 pg/ml. The 2-y overall survival rates for Groups 1, 2 and 3 were 33.3%, 60.0% and 93.9%, respectively., Conclusions: Higher serum concentrations of TNF-α, SCC and CA153 before therapy are independently associated with poor prognosis in patients with stage I and II disease. Combined usage of these three biomarkers allows efficient evaluation of outcomes in cervical cancer patients., (© 2013 Elsevier B.V. All rights reserved.)

Objective: The purpose of this article was to present the adenosquamous carcinoma (ASqC) of the pancreas: multidetector-row computed tomographic (CT) features and tumor characteristics., Materials and Methods: The clinical data and CT studies of 12 patients with pathologically proven ASqC of the pancreas between the dates February 2001 and February 2010 were retrospectively analyzed., Results: The presenting symptoms of ASqC of the pancreas were nonspecific. Elevated serum levels of carbohydrate antigen 19-9, carbohydrate antigen 12-5, and carcinoembryonic antigen were noted. The tumor was most commonly involved in the pancreatic head in 6 patients, with the dilation of the common bile duct and the upstream main pancreatic duct. All ASqCs exhibited invasive growth. No calcification and intratumoral hemorrhage were noted in ASqCs. Ten tumors showed enhancement in the early arterial phase and persistent enhancement in the portal vein phase., Conclusion: The typical CT appearance of ASqC was solitary oval or round without any capsule and a defined margin. The dilation of the main pancreatic duct and/or the common bile duct was always discovered. The huge infiltrative lesion outside the pancreas was detected in the tail and/or the body of the pancreas. Not only the elevation of carbohydrate antigen 19-9 is common, but also Ca12-5 and CEA, whereas human alpha fetoprotein elevation is not observed. The enhancement pattern of tumor showed persistence in the portal vein phase.

Purpose: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC)., Methods and Materials: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m2 twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received a maintenance dose of S-1 (80 mg/m2/day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity., Results: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of ≥100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy., Conclusions: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The most common pancreatic cancer is adenocarcinoma. Primary adenosquamous cell carcinoma of the pancreas is very rare and aggressive. A 46-year-old man presented with a 3-month history of dyspepsia and a 7-kg weight loss. The physical examination showed tenderness of the right upper quadrant of the abdomen. There was no jaundice. Amylase and lipase were elevated. CA 19-9 was elevated to 566.7 U/mL. Gastroduodenoscopy showed a hard ulceroinfiltrative mass with a yellowish exudate that bled readily on touch in the second portion of the duodenum. Abdominal computed tomography showed a 7.1 × 6.3-cm heterogeneously enhancing mass in the pancreatic head. The pancreatic mass had invaded the duodenum wall, gastric antrum, and gastroduodenal artery sheath. Fine-needle aspiration biopsy of the pancreatic mass revealed adenosquamous cell carcinoma, anaplastic type. We concluded that an adenosquamous cell carcinoma of pancreas had invaded the duodenal mucosa causing ulceration.

Cervical cancer is a leading cancer among women in developing countries. Infection with oncogenic human papillomavirus (HPV) types has been recognized as a necessary cause of this disease. Serum carotenoids and tocopherols have also been associated with risk for cervical neoplasia, but results from previous studies were not consistent. We evaluated the association of serum total carotene and tocopherols, and dietary intakes with the risk of newly diagnosed, histologically confirmed cervical intraepithelial neoplasia (CIN) grades 1, 2, 3 and invasive cancer in a hospital-based case-control study in São Paulo, Brazil. The investigation included 453 controls and 4 groups of cases (CIN1, n = 140; CIN2, n = 126; CIN3, n = 231; invasive cancer, n =108) recruited from two major public clinics between 2003 and 2005. Increasing concentrations of serum lycopene were negatively associated with CIN1, CIN3 and cancer, with odds ratios (OR) (95% CI) for the highest compared to the lowest tertile of 0.53 (0.27-1.00, p for trend = 0.05), 0.48 (0.22-1.04, p for trend = 0.05) and 0.18 (0.06-0.52, p for trend = 0.002), respectively, after adjusting for confounding variables and HPV status. Increasing concentrations of serum alpha- and gamma-tocopherols, and higher dietary intakes of dark green and deep yellow vegetables/fruit were associated with nearly 50% decreased risk of CIN3. These results support the evidence that a healthy and balanced diet leading to provide high serum levels of antioxidants may reduce cervical neoplasia risk in low-income women.

Gastric cancer (GC) is 1 of the most common human cancers. Early detection remains the most promising approach to improving long-term survival of patients with GC. We previously performed Serial Analysis of Gene Expression (SAGE) on 4 primary GCs and identified several GC-specific genes including Reg IV. Of these genes, olfactomedin 4 (OLFM4, also known as GW112 or hGC-1) is a candidate gene for cancer-specific expression. In this study, we examined the expression of olfactomedin 4 in human GC by immunohistochemistry. We also assessed serum olfactomedin 4 levels in GC patients by enzyme-linked immunosorbent assay. 94 (56%) of 167 GC cases were positive for olfactomedin 4 by immunostaining. Olfactomedin 4 staining was observed more frequently in stage I/II cases than in stage III/IV cases. The serum olfactomedin 4 concentration in presurgical GC patients (n = 123, mean +/- SE, 36.3 +/- 3.5 ng/mL) was significantly higher than that in healthy individuals (n = 76, 16.6 +/- 1.6 ng/mL). In patients with stage I GC, the sensitivity of serum olfactomedin 4 (25%) and Reg IV (35%) was superior to that of CA19-9 (5%) or CEA (3%). Furthermore, in patients with stage I GC, the combination of olfactomedin 4 and Reg IV elevated the diagnostic sensitivity to 52%. These results suggest that serum olfactomedin 4 is a useful marker for GC and its measurement alone or in combination with Reg IV has utility in the early detection of GC.

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

We report a rare case of adenosquamous carcinoma of the pancreas associated with humoral hypercalcemia of malignancy (HHM) in which parathyroid hormone-related protein (PTH-rP) was identified as the causative factor of hypercalcemia. A 72-year-old Japanese man was admitted to our institution complaining of fever and abdominal pain. Abdominal computed tomography demonstrated a large tumor in the body of the pancreas, with multiple liver metastases. Both serum calcium and PTH-rP levels were elevated. No accumulation was observed on bone scan with technetium-99. The patient died of pneumonia 3 months after admission. Autopsy demonstrated that the neoplasm in the pancreas showed an abrupt histological transition from adenocarcinoma to squamous cell carcinoma. PTH-rP was identified in the primary pancreatic tumor cells by immunohistochemical examination and a reverse-transcription polymerase chain reaction (RTPCR) method. We concluded that PTH-rP was the causative factor of the HHM, based on the laboratory data, immunohistochemical examination, and messenger RNA (mRNA) expression. This is a very rare report of adenosquamous cell carcinoma of the pancreas associated with HHM.

Oxidant/antioxidant balance has been suggested as an important factor for initiation and progression of cancer. In order to determine whether the degree of oxidative DNA damage and antioxidant enzyme activities in plasma obtained from patients with gastric and colon cancer who undergo resection can be used as a useful prognostic predictor, plasma level of 8-hydroxydeoxyguanosine (8-OHdG), activities of glutathione peroxidase (G-Px) and superoxide dismutase (SOD) were examined. 19 patients with gastric cancer and 26 patients with colon cancer who were undergoing resection of tumor were included by the study. Venous blood samples were taken just before the surgery. Plasma level of 8-OHdG was determined with ELISA, SOD and G-Px activities in plasma were measured by spectrophotometric kits. 8-OHdG level and activity of G-Px were found to be decreased, SOD activity was found to be increased in both gastric and colon cancer groups as compared to control group. Alpha fetoprotein was found to be correlated with G-Px in the gastric cancer group and correlated with 8-OHdG in the colon cancer group. SOD activity was correlated with CA-15-3 in the gastric cancer group. Low plasma level of 8-OHdG and altered antioxidant activity may implicate the deficient repair of oxidative DNA damage in patients with gastric and colon cancer. Those measured parameters were not found to be related with histopathological data but correlated with some tumor markers.

The efficacy and toxicity of mitomycin C (MMC), ifosfamide, and cisplatin in cervical cancer were evaluated. Between January 1997 and August 2003, 46 patients with locally recurrent, persistent, or disseminated cervical cancer were treated with MMC 6 mg/m(2), ifosfamide 3 g/m(2), and cisplatin 50 mg/m(2) (MIC regimen) repeated every 3 weeks (maximum six cycles). In eight patients (17%), the tumor involved the pelvis alone, in 11 (24%) the pelvis and extrapelvic sites, and 27 (59%) had only distant lesions. A total of 213 MIC cycles were administered (median six cycles per patient). Of the 44 evaluable patients, the overall response rate was 34% (9% complete and 25% partial responses). Median progression-free interval was 6 months (95% confidence interval [CI], 4-7 months), and overall survival was 10 months (95% CI, 6-14 months). Objective response was obtained in two patients (11%) with pelvic relapse within previously irradiated area and in 13 (50%) of those with extrapelvic lesions (P= 0.01). Leukopenia was seen in 59% of patients (grade 3 in 9%). Nonhematologic side effects were mild and relatively infrequent. In conclusion, MIC regimen provides satisfactory efficacy with acceptable toxicity in advanced cervical cancer patients. Better response is seen in lesions outside of the previously irradiated area.

CYFRA21 - 1, a fragment of cytokeratin19, has been widely assessed as a serum marker of squamous malignancies. Previous studies using CYFRA21 - 1 and SCC-Antigen have shown mixed results but have indicated a better predictive prognostic value for SCC-Ag as compared to CYFRA21-1. The aim of our prospective, observational, pilot study was to evaluate the role of CYFRA21-1 and SCC-Ag in primary cervical carcinoma. Pre-operative serum CYFRA21-1 and SCC-Ag were measured (n = 14) in women with cervical carcinoma and correlated with staging, clinico-pathological parameters and prognostic data. Logistic regression analysis with CYFRA 21 - 1 test status (positive or negative) as a dependent variable showed that nodal metastases (p = 0.001) and lymphovascular space invasion (LVSI) (p = 0.005) were significant predictors, whereas stage and SCC-Ag levels were not significant. There was also no statistically significant correlation between SCC-Ag and CYFRA21-1 levels. If larger studies confirm these preliminary results, the option of laparoscopic surgical staging in patients with raised CYFRA21-1 levels could be considered.

An autopsy case of adenosquamous pancreatic cancer in a 61-year-old male patient with an elevated serum level of parathyroid hormone-related protein (PTH-rP) is reported. He was admitted to our hospital with a 1-month-long history of abdominal discomfort and progressive abdominal fullness. A computed tomography (CT) scan of the abdomen showed a retroperitoneal mass, approximately 10 cm in diameter, involving the pancreas, with round enhancement on contrast examination. Histological examination of a specimen taken by CT-guided needle biopsy suggested squamous cell carcinoma or transitional cell carcinoma. Laboratory data on admission revealed a high serum calcium level and high PTH-rP level. The calcium level initially responded to intravenous hydration, furosemide, calcitonin, and bisphosphonates, decreasing from 15.0 to 9.0 mg/dl. However, the hypercalcemia recurred after 10 days. The patient developed carcinomatous peritonitis and acute renal failure, and died on the 25th hospital day. Autopsy revealed a mass in the pancreatic body to tail, invading the retroperitoneum, with progressive carcinomatous peritonitis. Histological examination of the mass revealed infiltrating carcinoma, showing squamous differentiation with focal intracytoplasmic lumina formation, consistent with pancreatic adenosquamous carcinoma. Immunohistological examination showed positive staining for PTH-rP. Adenosquamous carcinoma of the pancreas is relatively rare; only a few cases associated with hypercalcemia and for which PTH-rP has been identified as a causative factor have been reported. This is the first case in which immunohistochemistry proved localized PTH-rP in adenosquamous pancreatic cancer cells, associated with persistent hypercalcemia.

We report herein a rare case of esophageal carcinoma producing alpha-fetoprotein (AFP). A 69-year-old man presenting elevated AFP was admitted in order to investigate its origin, which several liver examinations done before admission had not revealed. At admission, his serum AFP was 76.9 ng/ml whereas other tumor markers were within normal range. As the patient complained of mild swallowing disturbance, gastrointestinal examinations were performed, and an esophageal carcinoma was found at the esophagogastric junction. The patient underwent subtotal esophagectomy and the esophagus was reconstructed by gastric tube. The postoperative course was uneventful and the serum AFP level normalized immediately after the operation. Histopathological examination demonstrated the tumor to be poorly-differentiated adenosquamous carcinoma, which contained scattered adenocarcinoma composed of clear cells positive to AFP by an immunohistochemical stain. The patient has been well for six months after the surgery without any sign of recurrence.

It is known that cell-free DNA circulates in plasma/serum of patients with cancer and that part of this DNA circulates as nucleosomes that can be quantified by ELISA. We analyzed the effect of tumor and chemotherapy upon the levels of nucleosomes in vitro, in vivo and in cervical cancer patients. The levels of nucleosomes pre- and post-treatment were correlated with response in 11 patients receiving chemotherapy. Nucleosomes were determined in nude mice treated with or without cisplatin and carrying tumors generated with HeLa cells, and in the cell lysate and supernatant of HeLa cells exposed to cisplatin in culture. In addition, nucleosomes were determined at different time points in patients and in rats receiving chemotherapy. Nucleosomes were higher in patients that controls (1,760 vs. 601, p = 0.0001). After 24 hr of treatment with oxaliplatin and gemcitabine, the levels decreased in 6 patients of whom 5 had response. Nucleosome levels differed between mice xenografted and not xenografted (765 vs. 378, p = 0.001) and between xenografted treated with or without cisplatin (650 vs. 765, p = 0.010), but not in tumor-free animals treated and untreated with cisplatin (378 vs. 379, p = 0.99). In vitro, nucleosomes reached at peak 8 hr in cell lysates to decrease thereafter, whereas in supernatant, levels continued to increase up to 24 hr. Serial determination of nucleosomes in patients showed a rise within 6-12 hr and then a reduction to below the basal at 24 hr. In rats, nucleosomes had no major changes in those receiving oxaliplatin or the triple combination of cisplatin, gemcitabine and paclitaxel as compared to untreated controls. An overdose of this triple combination produced a transient elevation of almost 1,000 AU over the basal. Our results demonstrate that most of circulating nucleosomes originate from the tumor and that chemotherapy produces an early rise most likely due to tumor apoptosis and that nucleosomes are rapidly cleared from circulation. On the contrary, chemotherapy within the therapeutic range of doses has no effect on nucleosome levels in healthy mice and rats. This data suggests that the determination of circulating nucleosomes pre- and post-treatment could be a useful test to predict response to chemotherapy in cancer patients., (Copyright 2003 Wiley-Liss, Inc.)

Estrogen receptor (ER) expression in human lung has been understudied, particularly in light of its potential biological importance in the female lung cancer epidemic. Reverse transcription-polymerase chain reaction was used to probe mRNA expression of wild-type ERalpha and ERbeta and their splice variants in human bronchogenic tumor and adjacent nontumor specimens. In tumor tissue from 13 women and 13 men, ERalpha was expressed in 85% of women versus 15% in men [P=0.001]. ERbeta was expressed equally in tumors from women versus men [92% vs. 69%, P=ns]. Both ERalpha and beta forms were expressed simultaneously in the lung tumors of 77% of women versus 15% of men [P=0.005]. Among adjacent nontumor lung specimens, 31% of the women expressed ERalpha mRNA versus 0% of men [P=0.101], and 39% of women expressed ERbeta mRNA versus 31% of men [P=ns]; only one woman and no men expressed both ERalpha and beta in nontumor tissue. Females expressed ERalpha [P=0.017], ERbeta [P=0.013], and ERalpha+beta [P=0.002] more frequently in tumor versus nontumor tissue, whereas in males expression of ERalpha, beta and both alpha+beta was not clearly different for tumor versus nontumor tissue. In specimens expressing ERalpha mRNA, the transcript lacking exon 7 (delta7) was the major splice variant with varying contributions from the transcripts delta4, delta3+4, delta5 and others unidentified. Alternative splicing of ERbeta mRNA was observed, but not to as great an extent as for ERalpha mRNA. ERalpha promoter usage in tumors varied among individuals. When the ER receptors were co-expressed in tumors, ERalpha was quantitatively more abundant in the majority of cases than ERbeta. Within this small group of 26 patients, no correlation was found between age, smoking history, plasma nicotine, cotinine, estradiol concentrations or histopathologic type with tumor or nontumor estrogen receptor status of any type. However, several positive correlations imply that: (1) ERalpha expression occurs more often in the lungs of women than men; (2) ERbeta is expressed with approximately equal frequency in the lungs of both genders; and (3) tumors display a higher frequency of both receptor types than nontumors in women. We hypothesize that these putative gender-dependent differences in ERalpha and ERbeta expression could contribute unique phenotypic characteristics to lung cancer development or progression in women.

Background: Serum levels of CA 19-9 correlate with survival among patients with pancreatic cancer treated with surgery or radiation therapy. In addition, CA 19-9 responses have been shown to predict for a better prognosis among patients with advanced disease treated with chemotherapy. The present study evaluates the predictive role of CA 19-9 pretreatment levels and response among patients treated with gemcitabine., Methods: We retrospectively identified 28 patients with advanced pancreatic cancer and baseline elevations of CA 19-9 (> 37 U/mL) who were treated with single agent gemcitabine. CA 19-9 response was defined as a > or = 50% decline at any time after treatment. Survival was estimated with the Kaplan-Meier method, and curves were compared with the log-rank test., Results: Eleven patients (39%) had a CA 19-9 response. The median survival of responding patients was longer than that of non-responding patients (13.8 vs 8 mo, p = .0272). When pretreatment CA 19-9 levels were analyzed, patients who had CA 19-9 below the median for the entire sample (1212 U/mL) lived significantly longer than patients with a CA 19-9 above the median (14.9 vs 7.4 mo, p = .0013). On multivariable analysis, pretreatment CA 19-9 level was an independent, and stronger predictor of survival (p = .0005) than CA 19-9 response (p = .0497). Other variables were not associated with survival., Conclusions: CA 19-9 may be a useful adjunct to response evaluation is this setting. In addition to CA 19-9 responses, prechemotherapy levels of this marker seem to have strong prognostic significance.

Background: The propensity of malignant tumors to increase in size, to invade locally and to metastasize is dependent on angiogenesis, which is induced by a variety of proteins including the family of fibroblast growth factors, vascular endothelial growth factor and angiogenin (ANG). The aim of the present study was to measure the serum levels of ANG in patients with CIN and invasive cervical cancer and to evaluate a possible correlation between ANG and various clinicopathologic parameters., Materials and Methods: Blood was collected from 62 patients with invasive cervical cancer and 47 patients with CIN. Serum samples of 30 age-matched healthy women acting as a control group were obtained. Determination of serum levels of ANG was performed using a quantitative human ANG immunoassay., Results: The overall median ANG serum level was 272.0 pg/ml (range 101.6-869.2). The median serum levels of ANG were 248.9 (range 101.6-307.2) for healthy female controls, 246.8 (range 169.7-468.1) for patients with CIN and 308.1 pg/ml (range 180.1-869.2) for patients with invasive cervical cancer. Serum levels of ANG were significantly elevated in patients with invasive cervical cancer compared with patients with CIN (p < 0.05) as well as healthy female controls (p < 0.05). No difference was found between ANG serum levels in women with CIN, and healthy controls (p < 0.05). No correlations were found between serum levels of ANG and clinico-pathologic parameters (p > 0.05)., Conclusions: Our data indicate the important role of ANG in tumor angiogenesis in invasive cervical cancer as ANG serum levels were significantly elevated in these patients. However, elevated ANG serum levels seem to occur only after the transformation from pre-invasive to invasive lesions.

Objective: The clinical value of tumor markers for early detection of recurrence was investigated in 32 patients with cervical adenocarcinoma or adenosquamous carcinoma who had recurrent tumors., Methods: Serum levels of CA 125, CA 19-9, carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCC), in addition to clinical status at the time of recurrence were investigated., Results: Among the 32 patients, 26 had no symptoms at the time of recurrence. In 20 patients, elevated serum levels of tumor markers were the first sign of recurrence. In 21 patients with recurrent adenocarcinoma, the positive rates were 14% (CA 125), 62% (CA 19-9), 29% (CEA), and 5% (SCC). There were 71% of cases positive for CA 19-9 and/or CEA. In 11 patients with recurrent adenosquamous carcinoma, the corresponding positive rates were 37% (CA 125), 46% (CA 19-9), 64% (CEA), and 55% (SCC), with 100% positive for CA 19-9, CEA, and/or SCC., Conclusions: The combination of CA 19-9 and CEA is probably the most promising for detection of recurrent cervical adenocarcinoma. For adenosquamous carcinoma, the additional use of SCC is recommended., (Copyright 2000 S. Karger AG, Basel.)

The relationship between preoperative serum carcinoembryonic antigen (CEA) level and treatment outcome for 39 clinical-stage I patients with surgically resected non-small-cell lung cancer (NSCLC) was retrospectively studied. Serum CEA levels were measured with an enzyme-linked immunosorbent assay kit, with the upper limit of normal defined as 6.7 ng/mL based on the 95% specificity level for benign lung disease in our hospital. Patients with serum CEA > or = 6.7 ng/mL (n = 9) were more likely to have advanced disease at surgery than those with serum CEA < 6.7 ng/mL (n = 30) (77.8% vs 16.7%, p = 0.0049). This increase in disease stage at surgery was mainly due to mediastinal lymph node metastasis. The sensitivity and specificity of serum CEA in the detection of pathological N2 disease were 62.5% and 87.1%, respectively. Survival for the high CEA group was significantly worse than that for the low CEA group (median survival time, 40.2 vs 75.8 months, p = 0.0125). Relapse-free survival for the high CEA group was also poorer than that of the low CEA group (p = 0.0032). In a multivariate analysis, serum CEA level was the most dominant factor affecting relapse-free survival (hazard ratio = 6.68, p = 0.0053). These findings suggest that preoperative serum CEA level is useful not only in detection of mediastinal lymph node metastasis, but also in prediction of survival for clinical-stage I patients with NSCLC.

We examined the expression of cytokeratin 20 (CK20) mRNA in the peripheral blood of oral squamous cell carcinoma (SCC) patients by reverse transcriptase polymerase chain reaction (RT-PCR). Eleven out of 12 oral SCC patients showed positive RT-PCR results. However, there is no clear relationship between the haematogenous CK20 mRNA and the metastasis. After initial treatment, all of the tumour-free survivors tested showed negative RT-PCR results. CK20 mRNA in peripheral blood can be used as a marker for tumour recurrence but not not for metastasis in oral SCC patients.

Preoperative evaluation of squamous cell carcinoma antigen (SCCa) was performed in 220 patients with surgically treated early-stage carcinoma of the cervix. The median duration of follow-up was 1.9 years. SCCa was significantly higher in tumors with a squamous element (P < 0.001). There was a squamous element in 171 tumors. SCCa was elevated (>2 ng/ml) in 21.6%. Significantly higher levels were associated with stage II disease (P < 0.001), tumors >4-cm size (P < 0.001), and lymph node metastases (P < 0.001). The positive predictive value for lymph node metastases at >2, >4, and >8.6 ng/ml SCCa is 51.4, 70.0, and 100% and the sensitivity is 58.1, 45.2, and 22.6%, respectively. Low SCCa is a poor predictor of absence of lymph node metastasis. The median SCCa for patients who developed tumor recurrence was greater than those who remained disease free (1.7 and 1.0 ng/ml, respectively, P = 0.009); however, in a multivariate analysis only lymph node metastasis and tumor size were of independent prognostic significance (P = 0.002 and P = 0.004, respectively). SCCa level >8.6 ng/ml is highly predictive of lymph nodal disease. There is no independent prognostic significance in patients with early-stage surgically treated cervical carcinoma.

Tissue polypeptide specific antigen (TPS) was measured by TPS ELISA in the sera of 88 patients with FIGO stage II and III cervical cancer and 93 healthy Thai women as the control group. The mean serum TPS levels were 63.1 U/L in the control group, and 166.4 and 363.2 U/L in stage II and III cervical cancer respectively. The mean of the control group and stage II patients were not significantly different while the mean of stage III patients was significantly different from those two groups (p < 0.0005). With the cut-off value of 90 U/L, the rates of TPS elevation were 22/35 (65.7%) in stage II and 42/53 (79.2%) in stage III patients. As for the pathology, squamous cell carcinoma showed a statistical difference from adenocarcinoma and adenosquamous carcinoma of P = 0.001. For squamous cell carcinoma, there was no difference between the keratinized and non-keratinized type (P = 0.451). TPS is not sensitive in stage II. However, it might be useful for predicting prognosis if the elevation is significantly high, and distant metastases or local recurrence should be investigated.

A case of primary adenosquamous carcinoma of the liver with an elevated level of serum squamous cell carcinoma related antigen is herein reported. Various hypotheses on the pathogenesis of adenosquamous carcinoma of the liver have been set forth previously, however there is still no widely accepted theory because of the absence of any sufficient evidence. The postoperative transition of serum squamous cell carcinoma related antigen and the immunohistochemical findings using anti-involucrin antigen in this case support the hypothesis that the squamous cell carcinoma component arises as a result of the metaplastic transformation of adenocarcinoma cells.

To clarify the significance of blood group antigen A (BAA) expression by neoplastic cells, we studied patients who had curative resections of stage I non-small cell lung carcinomas. Immunohistochemical staining using monoclonal antibodies was used to detect BAA expression by paraffin-embedded carcinoma cells. One hundred three patients were studied; mean age was 62.6 years, and 70 (68%) were male. Histologic types were as follows: adenocarcinoma, 52 (50.5%); squamous cell, 25 (24.3%); large cell, 24 (23.3%); and adenosquamous, 2 (1.9%). Histologic grades were as follows: I, 13 (12.6%); II, 26 (25.3%); and III, 64 (62.1%). All patients had American Joint Committee on Cancer stage I tumors: 65 patients (63.1%) had T1 tumors, and 38 (36.9%) had T2 tumors. Recurrences developed in 25 (24.3%) and metachronous malignancies in 4 (3.9%). Survival was 75% +/- 4.8% at 3 years and 66.6% +/- 7.5% at 5 years. Eighty-nine patients (86.4%) were blood group A and 14 (13.6%) were AB. Ninety-five (92.2%) were secretors of BAA and 8 (7.8%) were not. The expression of BAA by neoplastic cells was not detectable in 34 (33%), trace (1% to 5% of neoplastic cells) in 10 (9.7%), 1+ (6% to 25%) in 8 (7.8%), 2+ (26% to 50%) in 12 (11.7%), 3+ (51% to 75%) in 12 (11.7%), and 4+ (76% to 100%) in 27 (26.2%). The pattern of neoplastic cell staining was homogeneous in 14 patients (20.3%) and heterogeneous in 55 (79.7%). Carcinoma recurrence, overall survival, and event-free survival were not related to secretor status, BAA expression, or pattern of staining.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To report a rare manifestation of metastatic adenosquamous carcinoma of the colon in a patient presenting with humoral hypercalcaemia of malignancy mediated by parathyroid hormone related peptide (PTHrP)., Clinical Features: A 58-year-old man with metastatic adenosquamous carcinoma of the colon presented with hypercalcaemia. A technetium bone scan excluded osteolytic bone secondaries. A negative parathyroid subtraction scan and a low serum immunoreactive parathyroid hormone level (1-34 [amino acid fragment]) made the diagnosis of primary hyperparathyroidism unlikely. The diagnosis of humoral hypercalcaemia of malignancy was considered on the basis of an elevated serum PTHrP level and positive tumour immunoreactivity to PTHrP antiserum., Intervention and Outcome: The hypercalcaemia was effectively treated on two occasions with intravenous administration of aminohydroxy propilidene diphosphonate. Despite interventional chemotherapy, the patient died of progressive carcinomatosis., Conclusion: Hypercalcaemia is an extremely rare occurrence in carcinoma of the colon. This is the first documented case of humoral hypercalcaemia of malignancy associated with adenosquamous carcinoma of the colon mediated by PTHrP.

Relationship between the prevalence of the antibodies to HPV16E7 and L2 proteins and the development of cervical cancer was examined. Sera from 57 patients with invasive cervical cancer and from 200 age-matched healthy blood donors (16 to 64 years old) were examined for antibodies against E7 and L2 proteins of human papillomavirus (HPV) type 16. Bacterially expressed fusion antigens were used in a Western immunoblot assay. Ten (18%) of the patients and 10 (5%) of the controls were positive for only E7. Each eighteen of the patients (32%) and of the controls (9%) were positive for only L2. Three of the patients and 2 of the controls were positive for both E7 and L2 antibody reactivity. The patients' prevalence of antibodies for the E7 and L2 proteins was significantly higher than that of the controls (E7: chi 2 = 14.3, p < 0.01; L2: chi 2 = 23.8, p < 0.01). On the other hand, neither sex specific difference in the antibody prevalence was observed, nor was there any difference in the antibody prevalence with age. Our findings indicate that antibodies to the HPV16L2 proteins could be a parameter for cervical cancer development as well as those to the HPV16E7 proteins.