Evaluation of 95-Gene Classifier of Formalin-fixed Paraffin-embedded Tissues in ER-positive, HER2-negative, and Node-negative Breast Cancer.

BACKGROUND/AIM: A subset of patients with estrogen receptor (ER)-positive, HER2-negative, and node-negative breast cancer experience recurrences. Predicting patients who will have recurrences within 5 years of surgery is essential so that patients can be selected to receive adjuvant chemotherapy. The 95-gene classifier (95-GC) has been validated as a method to differentiate patients into high and low-risk groups for early recurrence. PATIENTS AND METHODS: In this study, we performed 95-GC analysis on 56 formalin-fixed paraffin-embedded (FFPE) tissue samples from patients who underwent surgery for ER-positive, HER2-negative, and node-negative breast cancer and did not receive adjuvant chemotherapy. We associated the obtained high- and low-risk groups with clinicopathological characteristics and recurrence-free survival (RFS). RESULTS: We classified 12 out of 56 patients into the high-risk recurrence group. We found significantly higher KI67 scores in patients in the high-risk group. Other clinicopathological characteristics were not associated with the 95-GC risk groups. Patients in the 95-GC low-risk group had a significantly better prognosis than those in the high-risk group (p=0.0387). The 5-year RFS rate was 97.6% in the low-risk group and 74.1% in the high-risk group, while the 10-year RFS rates were 90.1% and 74.1%, respectively. CONCLUSION: The 95-GC score can accurately predict RFS within 5 years of surgery for ER-positive, HER2-negative, and node-negative breast cancer using FFPE tissue samples. These prediction models could help assign patients to the most effective treatment regimen.

Diagnostic performance of diffusion weighted imaging of malignant and benign pulmonary nodules and masses: comparison with positron emission tomography.

BACKGROUND: Diffusion-weighted imaging (DWI) makes it possible to detect malignant tumors based on the diffusion of water molecules. However, it is uncertain whether DWI has advantages over FDG-PET for distinguishing malignant from benign pulmonary nodules and masses. MATERIALS AND METHODS: One hundred- forty-three lung cancers, 17 metastatic lung tumors, and 29 benign pulmonary nodules and masses were assessed in this study. DWI and FDG-PET were performed. RESULTS: The apparent diffusion coefficient (ADC) value (1.27 ± 0.35 ?10-3 mm2/sec) of malignant pulmonary nodules and masses was significantly lower than that (1.66 ± 0.58 ?10-3 mm2/sec) of benign pulmonary nodules and masses. The maximum standardized uptake value (SUV max: 7.47 ± 6.10) of malignant pulmonary nodules and masses were also significantly higher than that (3.89 ± 4.04) of benign nodules and masses. By using optimal cutoff values for ADC (1.44?10-3 mm2/sec) and for SUV max (3.43), which were determined with receiver operating characteristics curves (ROC curves), the sensitivity (80.0%) of DWI was significantly higher than that (70.0%) of FDG-PET. The specificity (65.5%) of DWI was equal to that (65.5%) of FDG-PET. The accuracy (77.8%) of DWI was not significantly higher than that (69.3%) of FDG- PET for pulmonary nodules and masses. As the percentage of bronchioloalveolar carcinoma (BAC) component in adenocarcinoma increased, the sensitivity of FDG-PET decreased. DWI could not help in the diagnosis of mucinous adenocarcinomas as malignant, and FDG-PET could help in the correct diagnosis of 5 out of 6 mucinous adenocarcinomas as malignant. CONCLUSIONS: DWI has higher potential than PET in assessing pulmonary nodules and masses. Both diagnostic approaches have their specific strengths and weaknesses which are determined by the underlying pathology of pulmonary nodules and masses.

Relationships between EGFR mutation status of lung cancer and preoperative factors - are they predictive?

BACKGROUND: The epidermal growth factor receptor (EGFR) mutation status of lung cancer is important because it means that EGFR-tyrosine kinase inhibitor treatment is indicated. The purpose of this prospective study is to determine whether EGFR mutation status could be identified with reference to preoperative factors. MATERIALS AND METHODS: One hundred-forty eight patients with lung cancer (111 adenocarcinomas, 25 squamous cell carcinomas and 12 other cell types) were enrolled in this study. The EGFR mutation status of each lung cancer was analyzed postoperatively. RESULTS: There were 58 patients with mutant EGFR lung cancers (mutant LC) and 90 patients with wild-type EGFR lung cancers (wild-type LC). There were significant differences in gender, smoking status, maximum tumor diameter in chest CT, type of tumor shadow, clinical stage between mutant LC and wild-type LC. EGFR mutations were detected only in adenocarcinomas. Maximum standardized uptake value (SUVmax:3.66±4.53) in positron emission tomography-computed tomography of mutant LC was significantly lower than that (8.26±6.11) of wild-type LC (p<0.0001). Concerning type of tumor shadow, the percentage of mutant LC was 85.7% (6/7) in lung cancers with pure ground glass opacity (GGO), 65.3%(32/49) in lung cancers with mixed GGO and 21.7%(20/92) in lung cancers with solid shadow (p<0.0001). For the results of discriminant analysis, type of tumor shadow (p=0.00036) was most significantly associated with mutant EGFR. Tumor histology (p=0.0028), smoking status (p=0.0051) and maximum diameter of tumor shadow in chest CT (p=0.047) were also significantly associated with mutant EGFR. The accuracy for evaluating EGFR mutation status by discriminant analysis was 77.0% (114/148). CONCLUSIONS: Mutant EGFR is significantly associated with lung cancer with pure or mixed GGO, adenocarcinoma, never-smoker, smaller tumor diameter in chest CT. Preoperatively, EGFR mutation status can be identified correctly in about 77 % of lung cancers.

Sensitive immunodetection of radiotoxicity after iodine-131 therapy for thyroid cancer using γ-H2AX foci of DNA damage in lymphocytes.

PURPOSE: The purpose of our study was to evaluate the degree of radiotoxicity to lymphocytes in thyroid cancer after iodine-131(I-131) therapy using γ-H2AX foci immunodetection. METHODS: This study focused on 15 patients who underwent I-131 therapy for differentiated thyroid cancer after surgery. All patients received 3.7 GBq of I-131. Venous blood samples were collected from each patient before therapy and 4 days thereafter. Lymphocytes were isolated from the blood samples and subjected to γ-H2AX immunofluorescence staining. RESULTS: The number (mean ± SD) of foci per lymphocyte nucleus was 0.41 ± 0.51 before and 6.19 ± 1.80 after radioiodine therapy, and this difference was statistically significant (P = 0.001 < 0.05). Absorbed doses estimated for the 15 patients were 0.77 ± 0.31 Gy applying standard line in vitro external radiation doses. CONCLUSION: γ-H2AX foci immunodetection in lymphocytes may detect radiation-induced DNA damage associated with I-131 therapy for thyroid cancer, and may facilitate estimation of the radiation doses absorbed with this therapy.

Advantages of diffusion-weighted imaging over positron emission tomography-computed tomography in assessment of hilar and mediastinal lymph node in lung cancer.

BACKGROUND: The significance of diffusion-weighted imaging (DWI) is uncertain for the diagnosis of nodal involvement. The purpose of this study was to examine diagnostic capability of DWI compared with PET-CT for nodal involvement of lung cancer. METHODS: A total of 160 lung cancers (114 adenocarcinomas, 36 squamous cell carcinomas, and 10 other cell types) were analyzed in this study. DWI and PET-CT were performed preoperatively. RESULTS: The optimal cutoff values to diagnose metastatic lymph nodes were 1.70 × 10(-3) mm(2)/s for ADC value and 4.45 for SUVmax. DWI correctly diagnosed N staging in 144 carcinomas (90 %) but incorrectly diagnosed N staging in 16 (10 %) [3 (1.9 %) had overstaging, 13 (8.1 %) had understaging]. PET-CT correctly diagnosed N staging in 133 carcinomas (83.1 %) but incorrectly diagnosed N staging in 27 (16.8 %) [4 (2.5 %) had overstaging, 23 (14.4 %) had understaging]. Sensitivity, accuracy, and negative predictive value for N staging by DWI were significantly higher than those by PET-CT. Of the 705 lymph node stations examined, 61 had metastases, and 644 did not. The maximum diameter of metastatic lesions in lymph nodes were 3.0 ± 0.9 mm in 21 lymph node stations not detected by either DWI or PET-CT: 7.2 ± 4.1 mm in 39 detected by DWI, and 11.9 ± 4.1 mm in 24 detected by PET-CT. There were significant differences among them. The sensitivity (63.9 %) for metastatic lymph node stations by DWI was significantly higher than that (39.3 %) by PET-CT. The accuracy (96.2 %) for all lymph node stations by DWI was significantly higher than that (94.3 %) by PET-CT. CONCLUSIONS: DWI has advantages over PET-CT in diagnosing malignant from benign lymph nodes of lung cancers.

Diffusion-weighted imaging is superior to positron emission tomography in the detection and nodal assessment of lung cancers.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (DWI) makes it possible to detect malignant tumors based on the difference in the diffusion of water molecules among tissues. The aims of this study are to examine the usefulness of DWI compared with positron emission tomography-computed tomography (PET-CT) in the assessment of lung cancer, and the relationships between the apparent diffusion coefficient (ADC) value and several pathologic factors. METHODS: Sixty-three patients with primary non-small cell lung cancer were enrolled in this study. The DWI and PET-CT were performed before surgery. There were 42 adenocarcinomas, 19 squamous cell carcinomas, and 2 other cell types. RESULTS: Sixty-one lung cancers (97%) were detected visually with DWI. This was significantly higher than 54 lung cancers (86%) with PET-CT. The accuracy for N staging by DWI was 0.81 (51 of 63), which was not significantly higher than 0.71 (45 of 63) by PET-CT. The sensitivity (0.75) for individual metastatic lymph node stations by DWI was significantly higher than that (0.48) by PET-CT. The specificity for individual nonmetastatic lymph node stations was 0.99 by DWI and 0.97 by PET-CT, respectively. The accuracy (0.95) for the diagnosis of lymph node stations by DWI was significantly higher than that (0.90) by PET-CT. There was a weak reverse relationship (correlation coefficient: 0.286) between the ADC value and the maximum standardized uptake value, but no relationship between ADC value and tumor size. The ADC values increased while the cell differentiation increased. CONCLUSIONS: Diffusion-weighted magnetic resonance imaging is superior to PET-CT in the detection of primary lesions and nodal assessment of non-small cell lung cancers.