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There have been several epidemiological studies of the association between 25-hydroxyvitamin D (25(OH)D) level and lung cancer risk. We explored the potential association between serum 25(OH)D levels and mutations in epidermal growth factor receptor (EGFR) in patients with pulmonary adenocarcinoma. We analyzed clinical data from 135 patients whose serum 25(OH)D levels were measured and EGFR mutational status was tested at the time of diagnosis. The relationship between 25(OH)D and clinical factors such as EGFR mutational status and sex was examined. The median serum 25(OH)D level in patients with pulmonary adenocarcinoma was 16.8 ng/ml (range: 3.0-84.3 ng/ml). The level of 25(OH)D was lower in female patients than in male patients (P=0.03). Interestingly, 25(OH)D levels of patients with EGFR-mutated tumors were low compared with those with wild-type tumors (median 18.2 vs 14.7 ng/ml, P=0.011). After a dose-response relationship between EGFR mutations and 25(OH)D levels (as a continuous variable) was observed (OR = 0.96, P = 0.036), we categorized 25(OH)D levels as low (<16.8 ng/ml) and high ( >16.8 ng/ml). Multivariate analysis revealed the association between low 25(OH)D levels and a high incidence of EGFR mutations (adjusted OR = 2.42, 95% CI: 1.11-5.26, P=0.026). The results from this study indicate that low 25(OH)D levels are associated with EGFR mutations in pulmonary adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: There has been an increase in the use of fine needle aspiration cytology (FNAC) for the diagnosis of parathyroid lesions (PLs). Differentiation between a thyroid lesion and a PL is not easy because of their similar features. We reviewed parathyroid aspirates in our institution and aimed to uncover trends in diagnostic criteria. Methods: We selected 25 parathyroid aspirates (from 6 men and 19 women) confirmed surgically or immunohistochemically from 2006 to 2011. Results: Major architectural findings of PLs include scattered naked nuclei, loose clusters, a papillary pattern with a fibrovascular core, tight clusters, and a follicular pattern. These architectures were commonly admixed with one another. Cytological features included anisokaryosis, stippled chromatin, a well-defined cell border, and oxyphilic cytoplasm. Eighteen of the 25 patients were diagnosed with PL using FNAC. Seven patients had been misdiagnosed with atypical cells (n=2), benign follicular cells (n=2), adenomatous goiter (n=2) and metastatic carcinoma (n=1) in FNAC. Using clinicoradiologic data, the sensitivity of the cytological diagnosis was 86.7%. The cytological sensitivity decreased to 50% without this information. Conclusions: FNAC of PL is easily confused with thyroid lesions. A combination of cytological parameters and clinical data will be required to improve the diagnostic sensitivity of PLs. [ABSTRACT FROM AUTHOR]

Purpose: We performed a pilot study to determine the benefit of high-dose chemotherapy and autologous peripheral blood stem cell transplantation (HDCT/autoPBSCT) for patients with Ewing sarcoma family of tumors. Methods: We retrospectively analyzed the data of patients who received HDCT/autoPBSCT at Korea Cancer Center Hospital. Patients with relapsed, metastatic, or centrally located tumors were eligible for the study. Results: A total of 9 patients (3 male, 6 female), with a median age at HDCT/autoPBSCT of 13.4 years (range, 7.1 to 28.2 years), were included in this study. Patients underwent conventional chemotherapy and local control either by surgery or radiation therapy, and had achieved complete response (CR, n=7), partial response (n=1), or stable disease (n=1) prior to HDCT/autoPBSCT. There was no transplant-related mortality. However, the median duration of overall survival and event-free survival after HDCT/autoPBSCT were 13.3 months (range, 5.3 to 44.5 months) and 6.2 months (range, 2.1 to 44.5 months), respectively. At present, 4 patients are alive and 5 patients who experienced adverse events (2 metastasis, 2 local recur, and 1 progressive disease) survived for a median time of 2.8 months (range, 0.1 to 10.7 months). The 2-year survival after HDCT/autoPBSCT was 44.4%±16.6% and disease status at the time of HDCT/autoPBSCT tended to influence survival (57.1%±18.7% of cases with CR vs. 0% of cases with non-CR, P =0.07). Conclusion: Disease status at HDCT/autoPBSCT tended to influence survival. Further studies are necessary to define the role of HDCT/autoPBSCT and to identify subgroup of patients who might benefit from this investigational treatment [ABSTRACT FROM AUTHOR]

Purpose Features of epidermal growth factor receptor (EGFR) expression in osteosarcoma and in vitro efficacies of EGFR inhibitors against osteosarcoma cells were evaluated. Materials and Methods Thirty biopsy samples of osteosarcoma patients were retrospectively analyzed for EGFR protein expression by immunohistochemistry. Relationships between EGFR expression and clinicopathologic characteristics and treatment outcomes were evaluated. Four osteosarcoma cell lines were analyzed for EGFR and p-EGFR expression by western blotting. Efficacies of gefitinib and BIBW2992 on osteosarcoma cells were evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Tyrosine kinase domains in exons 18 to 21 were sequenced and gene expression analyses of EGFR and PTEN were performed in four osteosarcoma cell lines. Results EGFR protein was expressed in 27 (90%) samples (6 low, 12 intermediate, 9 high) and in three cell lines. Intermediate or high staining for EGFR was related to a tumor volume < 150 mL (p < 0.001) and histologic subtype other than osteoblastic type (p=0.03). However, EGFR expression was not associated with histologic response to preoperative chemotherapy or survival. Gefitinib and BIBW 2992 did not have any significant inhibitory effect on cell viabilities. DNA sequencing analysis revealed three osteosarcoma cell lines have single base changes at codon 2361 of exon 20 (G to A), without affecting translation results. Furthermore, no mutation was found to be associated with constitutive EGFR activation. Conclusion In the present study, gefitinib and BIBW2992 were not effective against osteosarcoma cells. However, as osteosarcoma cells express EGFR, further studies are necessary to explore the potential of other therapeutic agents targeting EGFR. [ABSTRACT FROM AUTHOR]

Purpose: We did this retrospective study to explore the association between epidermal growth factor receptor (EGFR) mutation and clinical features in postoperative recurrent female non-small-cell lung cancer (NSCLC). Materials and Methods: We reviewed clinical data on 86 female patients who had postoperative recurrent disease between December 1992 and July 2007. The start of tyrosine kinase inhibitor therapy was treated as a censoring event. Corresponding surgical specimens of primary tumors were used to test for EGFR mutations. Results: Thirty patients presented with local recurrence and distant recurrence was identified in 56. Thirty-four of the 86 patients (40%) harbored EGFR mutations. Patients with distant recurrence were more likely to have EGFR mutations than patients with local recurrence (48% versus 23%; P = 0.024). On multivariate analysis, distant recurrence was associated with a high frequency of EGFR mutations (OR, 3.3; P = 0.028). Survival analysis showed poor survival of patients with mutated EGFR (HR, 2.3; P = 0.017) or with non-adenocarcinoma histology (HR, 3.3; P = 0.001). Conclusion: The association between recurrence pattern and EGFR mutation status was suggested in recurrent female NSCLC patients. In addition, our data indicate unfavorable disease process of EGFR mutated tumors. Further studies need to be conducted to validate these findings. [ABSTRACT FROM AUTHOR]

Synovial sarcoma arises in the para-articular tissues, and it can also occur in various unexpected sites. We report a rare case of primary monophasic synovial sarcoma (MSS) arising in the mesentery. A 59-year-old man presented with a palpable abdominal mass. On microscopic examination, the entire tumor comprised a dense proliferation of the spindle cells without epithelial components. The tumor cells were positive for transducin-like enhancer of split 1, bcl-2, epithelial membrane antigen and CD99 but negative for CD34, CD117, alpha-smooth muscle actin, cytokeratin, and calretinin on immunohistochemistry. The reverse transcriptase-polymerase chain reaction revealed a single 151-bp fragment representing the SYT-SSX2 fusion transcript. Because mesenteric MSS is extremely rare and many cases display histologic findings that overlap with those of more frequently involved tumors such as hemangiopericytoma and gastrointestinal stromal tumor, there is a chance of making an incorrect diagnosis that can result in an inappropriate treatment. [ABSTRACT FROM AUTHOR]

We performed this retrospective study to assess the association of epidermal growth factor receptor (EGFR) with metastatic presentations in advanced non-small cell lung cancer (NSCLC). The data from 125 patients with stage III or IV NSCLC were analyzed. We detected EGFR mutations in 36 NSCLC patients. EGFR mutations were predominant in never-smokers (P < .001), patients with adenocarcinomas (P < .001), and female patients (P < .001). When the metastatic sites were analyzed, pleural metastases were associated with a high incidence of EGFR mutations (P = .028). Particularly, pleural metastases with minimal effusion (PMME) were associated with EGFR mutational status (P = .001). Patients with N3 lesions were less likely to harbor EGFR mutations (P = .033). On multivariate analysis, N3 lesions (P = .017) and PMME (P < .001) remained significant factors for EGFR mutations. EGFR mutations may be associated with different presentations of pleural and N3 nodal metastases. [ABSTRACT FROM AUTHOR]

In this retrospective study, we assessed tumor growth patterns as visualized on MR images, and examined whether tumor growth patterns correlate with clinicopathologic variables. In addition, we also evaluated the relationship between patient outcome and tumor growth pattern in the whole study cohort and in subsets of AJCC IIA and IIB patients. We retrospectively reviewed 347 patients with Enneking stage IIB and AJCC stage II osteosarcoma that was treated with surgery and neoadjuvant chemotherapy at our institute. Patients were divided into three groups based on tumor growth pattern, namely, concentric, eccentric, and longitudinal groups. Fisher’s exact test was performed to analyze correlations between tumor growth patterns and clinicopathological variables. Five-year metastasis-free survival and overall survival were evaluated using univariate and multivariate analyses. In terms of tumor growth patterns, 225 patients (64.8%) had a concentric, 71 (20.5%) an eccentric and 51 (14.7%) a longitudinal tumor. Eccentric tumors were usually small and responded well to chemotherapy, whereas concentric tumors were large and responded poorly. The prognostic significances of tumor growth patterns were confirmed by univariate and multivariate analyses. Among AJCC stage IIA patients, no survival difference was found according to growth pattern, whereas in AJCC stage IIB patients, longitudinal tumors were associated with significantly better survival than concentric tumors. Tumor growth pattern was found to be an independent prognostic factor in stage II osteosarcoma. Moreover, longitudinally growing tumors were associated with better survival in AJCC stage IIB patients. Our results suggest that tumor growth pattern could be used as an indicator of risk-adapted therapy when combined with other prognostic factors. [ABSTRACT FROM AUTHOR]

Abstract Objective  In this retrospective study, we assessed the plain-film radiographic patterns of American Joint Committee on Cancer (AJCC) stage II osteosarcoma and analyzed the relationship between these patterns and clinicopathologic variables. Materials and methods  We retrospectively reviewed 347 patients with AJCC stage II osteosarcoma who were treated at our institute. Patients were divided into three groups based on radiographic patterns, i.e., osteoblastic, osteolytic, and mixed. Fisher’s exact chi-square test was performed to analyze correlations between radiographic patterns and clinicopathological variables. Results  One hundred and eighty-eight patients had an osteoblastic tumor, 101 had an osteolytic tumor, and 58 had a mixed tumor. Tumors with an osteoblastic pattern showed a tendency to have the following characteristics: AJCC stage II-B, osteoblastic or chondroblastic subtype, and no pathologic fracture. Conversely, osteolytic tumors were frequently of AJCC stage II-A, had a fibroblastic or rare subtype, and were associated with a pathologic fracture. Finally, mixed tumors were frequently found in men. No survival difference was found according to radiographic pattern. Conclusions  Plain-film radiographic patterns were found to be related with clinicopathological features. We believe that it could be used to provide valuable information for treatment decision-making in cases of high-grade extremity osteosarcoma. [ABSTRACT FROM AUTHOR]

Abstract Background To propose a personalized therapeutic approach in osteosarcoma treatment, we assessed whether sequential [18F]FDG PET/CT (PET/CT) could predict the outcome of patients with osteosarcoma of the extremities after one cycle and two cycles of neoadjuvant chemotherapy. Methods A total of 73 patients with AJCC stage II extremity osteosarcoma treated with 2 cycles of neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy were retrospectively analyzed in this study. All patients underwent PET/CT before (PET0), after 1 cycle (PET1), and after the completion of neoadjuvant chemotherapy (PET2), respectively. Maximum standardized uptake value (SUVmax) (corrected for body weight) and the % changes of SUVmax were calculated, and histological responses were evaluated after surgery. Receiver-operating characteristic (ROC) curve analyses and the Cox proportional hazards models were used to analyze whether imaging and clinicopathologic parameters could predict event-free survival (EFS). Results A total of 36 patients (49.3%) exhibited a poor histologic response and 17 patients (23.3%) showed events (metastasis in 15 and local recurrence in 2). SUVmax on PET2 (SUV2), the percentage change of SUVmax between PET0 and PET1 (Δ%SUV01), and between PET0 and PET2 (Δ%SUV02) most accurately predicted events using the ROC curve analysis. SUV2 (relative risk, 8.86; 95% CI, 2.25–34.93), Δ%SUV01 (relative risk, 5.97; 95% CI, 1.47–24.25), and Δ%SUV02 (relative risk, 6.00; 95% CI, 1.16–30.91) were independent predicting factors for EFS with multivariate analysis. Patients with SUV2 over 5.9 or Δ%SUV01 over − 39.8% or Δ%SUV02 over − 54.1% showed worse EFS rates than others (p < 0.05). Conclusions PET evaluation after 1 cycle of presurgical chemotherapy can predict the clinical outcome of extremity osteosarcoma. [18F]FDG PET, which shows a potential role in the early evaluation of the modification of timing of local control, can be a useful modality for early response monitoring of neoadjuvant chemotherapy.

BACKGROUND: The level of proliferation activity is a strong prognostic or predictive indicator in breast cancer, but its optimal measurement is still in debate, necessitating new proliferation markers. In the present study, the prognostic significance of the CKAP2-positive cell count (CPCC), a new proliferation marker, was evaluated, and the results were compared with those for the mitotic activity index (MAI). METHODS: This study included 375 early-stage breast cancer samples collected from two institutions between 2000 and 2006. Immunohistochemical staining was performed using a CKAP2 monoclonal antibody. Cox proportional hazard regression models were fitted to determine the association between the CPCC and relapse-free survival (RFS) amongst three groups formed on the basis of the CPCC or MAI value: groups 2 and 3 showing the middle and highest values, respectively, and group 1 the lowest. RESULTS: After adjustment for age, T stage, N stage, HER2 status, estrogen receptor status, progesterone receptor status, institution, and year of surgical resection, the CPCC was associated with a significantly worse RFS {hazard ratio [HR] = 4.10 (95% CI: 1.64-10.29) for group 2; HR = 4.35 (95% CI: 2.04-10.35) for group 3}. Moreover, its prognostic significance was similar to or higher than that based on the MAI {HR = 2.05 (95% CI: 0.94-4.65) for group 2; HR = 2.35 (95% CI: 1.09-5.10) for group 3}. In subgroup analyses, the CPCC showed a prognostic significance in the luminal A and triple-negative subgroups, but not in the HER2-positive subgroup. CONCLUSIONS: Chromatin CKAP2 is an independent prognostic marker for RFS in early-stage breast cancer, and could potentially replace the MAI in clinical evaluation of proliferation activity. Additionally, our study results suggest that the prognostic significance of proliferation activity differs among the various subgroups of breast cancer.