Correlation Between Quantitative Spectral CT Parameters and Ki-67 Expression in Lung Adenocarcinomas Manifesting as Ground-glass Nodules.

OBJECTIVE: We assessed the feasibility of spectral CT imaging for diagnosing lung adenocarcinomas manifesting as ground-glass nodules (GGNs) with varying Ki-67 expression. METHODS: Spectral CT parameters in 116 patients with lung adenocarcinomas manifesting as GGNs were analyzed. Cases were grouped into pre-invasive/minimally invasive adenocarcinoma (pre/MIA) and invasive adenocarcinoma (IA) groups. The Ki-67 labeling index (Ki-67 LI) was measured and compared between the two groups. Ki-67 LI was divided into three grades based on the number of positive-stained cells. Spectral CT parameters (diameter, water, and iodine concentrations of the lesion [WCL and ICL], the slope of the spectral Hounsfield unit curve [λHU], and CT values from 40 to 140 keV [at 10 keV intervals]) were compared among the three different grades. The correlation between quantitative spectral CT imaging parameters and Ki-67 LI was analyzed using Spearman correlation analysis. RESULTS: Ki-67 LI in the IA group was significantly higher than in the pre/MIA group (p < 0.01). Grade 2 had higher diameter, WCL, and monochromatic CT values, and grade 1 had higher ICL and λHU. The WCL and monochromatic CT values were highly and positively correlated with Ki-67 LI. CT40keV had the highest correlation with Ki-67 LI, the diameter was moderately correlated with Ki- 67 LI, and ICL and λHU were weakly correlated with Ki-67 LI. CONCLUSION: Spectral CT, a noninvasive diagnostic method, is valuable for predicting Ki-67 expression higher in IA, thus allowing preoperative evaluation of lung adenocarcinomas manifesting as GGNs.

Association between quantitative spectral CT parameters, Ki-67 expression, and invasiveness in lung adenocarcinoma manifesting as ground-glass nodules.

BACKGROUND: Few studies about lung ground-glass nodules (GGNs) have been done using non-enhancement spectral computed tomography (CT) imaging. PURPOSE: To examine the association between spectral CT parameters, Ki-67 expression, and invasiveness in lung adenocarcinoma manifesting as GGNs. MATERIAL AND METHODS: Spectral CT parameters were analyzed in 106 patients with lung GGNs. The Ki-67 labeling index (Ki-67 LI) was measured, and patients were divided into low expression and high expression groups according to the number of positive-stained cells (low expression ≤10%; high expression >10%). Spectral CT parameters were compared between low and high expression groups. The correlation between spectral CT parameters and Ki-67 LI was estimated by Spearman correlation analysis. Cases were divided into a preinvasive and minimally invasive adenocarcinoma (MIA) group (atypical adenomatous hyperplasia, adenocarcinoma in situ, and MIA) and invasive adenocarcinoma (IA) group. Spectral CT parameters were compared between the two groups. The diagnostic performance was evaluated using receiver operating characteristic analysis. RESULTS: There were significant differences in water concentration of lesions (WCL) and monochromatic CT values between the low and high expression groups. CT 40 keV had the highest correlation coefficient with Ki-67 LI. WCL and monochromatic CT values were significantly higher in the IA group than in the pre/MIA group. The value of area under the curve of CT 40 keV was 0.946 (95% confidence interval=0.905-0.988) for differentiating the two groups; the cutoff was -280.66 Hu. CONCLUSION: Spectral CT is an effective non-invasive method for the prediction of proliferation and invasiveness in lung adenocarcinoma manifesting as GGNs.

Expression of and correlation between BCL6 and ZEB family members in patients with breast cancer.

B-cell lymphoma 6 (BCL6), a proto-oncogene, is an evolutionarily conserved zinc finger protein that functions as a transcriptional repressor. BCL6 is the master regulator of B-lymphocyte development, and it has been reported that BCL6 may serve an important role in breast cancer progression. The aim of the present study was to investigate the expression of BCL6, zinc finger E-box-binding homeobox (ZEB)1 and ZEB2 and their associations in breast cancer. The mRNA and protein expression of BCL6, ZEB1 and ZEB2 was assessed using in situ hybridization and immunohistochemistry, respectively, in 228 patients with breast cancer and 80 patients with benign breast disease. In addition, the association between BCL6, ZEB1 and ZEB2 expression and the clinicopathological characteristics and survival of patients with breast cancer were analyzed. The mRNA and protein expression of BCL6, ZEB1 and ZEB2 were significantly higher in breast cancer tissues compared with benign breast disease tissues (P<0.05). The expression of BCL6, ZEB1 and ZEB2 were significantly positively correlated with tumor size, lymph node metastasis and a higher tumor stage (P<0.05). Furthermore, patients with BCL6, ZEB1 and ZEB2 protein-positive primary tumors had significantly lower overall survival (P=0.001, 0.002 and 0.001, respectively) and relapse-free survival (P=0.002, 0.001 and 0.003, respectively) rates. The mRNA expressions of ZEB1 (rs=0.326, P<0.001) and ZEB2 (rs=0.382, P<0.001) were significantly positively correlated with BCL6 mRNA expression, and the protein expressions of ZEB1 ((rs=0.449, P<0.001) and ZEB2 (rs=0.669, P<0.001) were significantly positively correlated with BCL6 protein expression. These results suggest that BCL6, ZEB1 and ZEB2 are potential biomarkers for the invasion, metastasis and prognosis of breast cancer, and that BCL6 may be a regulator of the ZEB family.

Expression and correlation of Twist and gelatinases in breast cancer.

Altered expression of Twist, matrix metalloproteinase (MMP)-2 and MMP-9 proteins has been identified in various types of human cancers. However, the correlation between Twist and these gelatinases in breast cancer remains unclear. In this study, immunohistochemical analysis of Twist, MMP-2 and MMP-9 expression was performed on tissue microarrays from 200 breast cancer cases. The association of Twist and gelatinase expression with clinicopathological factors and patient survival was analyzed. Altered expression of Twist, MMP-2 and MMP-9 proteins was observed in breast cancer tissue. The positive rates of Twist, MMP-2 and MMP-9 protein expression were 75.5, 97.0 and 96.0%, respectively. Increased expression of Twist was positively correlated with the status of axillary lymph node metastasis and higher tumor-node-metastasis (TNM) stage (P<0.01). Moreover, increased expression of Twist was correlated with poor overall survival (OS) and post-operative relapse-free survival (RFS), compared with those for the patients with reduced expression levels of Twist (P<0.05, P<0.01). The expression of MMP-2 and MMP-9 was positively correlated with Twist expression (P<0.001). Our results indicate that Twist may play an important role in the invasion, metastasis and prognosis of breast cancer. Additionally, our results suggest that Twist may be a regulator of gelatinases (MMP-2 and MMP-9).

Correlation between target motion and the dosimetric variance of breast and organ at risk during whole breast radiotherapy using 4DCT.

PURPOSE: The purpose of this study was to explore the correlation between the respiration-induced target motion and volume variation with the dosimetric variance on breast and organ at risk (OAR) during free breathing. METHODS AND MATERIALS: After breast-conserving surgery, seventeen patients underwent respiration-synchronized 4DCT simulation scans during free breathing. Treatment planning was constructed using the end inspiration scan, then copied and applied to the other phases and the dose distribution was calculated separately to evaluate the dose-volume histograms (DVH) parameters for the planning target volume (PTV), ipsilateral lung and heart. RESULTS: During free breathing, the treated breast motion vector was 2.09 ± 0.74 mm, and the volume variation was 3.05 ± 0.94%. There was no correlation between the breast volume and target/OAR dosimetric variation (|r| = 0.39 ~ 0.48). In the anteroposterior, superoinferior and vector directions, breast movement correlated well with the mean PTV dose, conformal index, and the lung volume receiving high dose (|r| = 0.651-0.975); in the superoinferior and vector directions, breast displacement only correlated with the heart volume receiving >5 Gy (V5) (r = -0.795, 0.687). The lung volume and the lung volume receiving high dose correlated reasonably well (r = 0.655 ~ 0.882), and a correlation only existed between heart volume and V5 (r = -0.701). CONCLUSION: Target movement correlated well with the target/OAR dosimetric variation in certain directions, indicating that whole breast IMRT assisted by breathing control or respiratory-adapted gated treatment promotes the accuracy of dose delivery during radiotherapy. During free breathing, the effect of breast volume variation can be ignored in whole breast IMRT.

Evaluation of dosimetric variance in whole breast forward-planned intensity-modulated radiotherapy based on 4DCT and 3DCT.

This study was performed to explore and compare the dosimetric variance caused by respiratory movement in the breast during forward-planned IMRT after breast-conserving surgery. A total of 17 enrolled patients underwent the 3DCT simulation scans followed by 4DCT simulation scans during free breathing. The treatment planning constructed using the 3DCT images was copied and applied to the end expiration (EE) and end inspiration (EI) scans and the dose distributions were calculated separately. CTV volume variance amplitude was very small (11.93 ± 28.64 cm(3)), and the percentage change of CTV volumes receiving 50 Gy and 55 Gy between different scans were all less than 0.8%. There was no statistically significant difference between EI and EE scans (Z =-0.26, P = 0.795). However, significant differences were found when comparing the Dmean at 3DCT planning with the EI and EE planning (P = 0.010 and 0.019, respectively). The homogeneity index at EI, EE and 3D plannings were 0.139, 0.141 and 0.127, respectively, and significant differences existed between 3D and EI, and between 3D and EE (P = 0.001 and 0.006, respectively). The conformal index (CI) increased significantly in 3D treatment planning (0.74 ± 0.07) compared with the EI and EE phase plannings (P = 0.005 and 0.005, respectively). The V30, V40, V50 and Dmean of the ipsilateral lung for EE phase planning were significantly lower than for EI (P = 0.001-0.042). There were no significant differences in all the DVH parameters for the heart among these plannings (P = 0.128-0.866). The breast deformation during respiration can be disregarded in whole breast IMRT. 3D treatment planning is sufficient for whole breast forward-planned IMRT on the basis of our DVH analysis, but 4D treatment planning, breath-hold, or respiratory gate may ensure precise delivery of radiation dose.

[Evaluation of dosimetric variance in forward intensity modulated radiotherapy of the breast based on 4D CT and 3D CT during free breathing].

OBJECTIVE: To explore the dosimetric variance in forward intensity modulated radiotherapy (IMRT) based on 4D CT and 3D CT after breast conserving surgery. METHODS: Seventeen patients after breast conserving surgery underwent 3D CT simulation scans followed by respiration-synchronized 4D CT simulation scans at free breathing state. The treatment plan constructed using the end inspiration (EI) scan was then copied and applied to the end expiration (EE), and 3D scans and dose distribution were calculated separately. Dose-volume histograms (DVHs) parameters for the CTV, PTV, ipsilateral lung and heart were evaluated and compared. RESULTS: The CTV volume difference was biggest between T0 and 3D CT, and the volume difference was 4.10 cm(3). Mean dose of PTV at EE was lower than that at EI (P = 0.019), but there were no statistically significant difference between 3D and EI, EE (all P > 0.05). The homogeneity index (HI) at EI, EE, 3D plans were 0.149, 0.159 and 0.164, respectively, and a significant difference was only between EI and EE (P = 0.039). The highest conformal index (CI) was at EI phase (P < 0.05), and there was no significant difference between EE and 3D (P = 0.758). The V(40) and V(50) of ipsilateral lung at EE phase were lower than that at EI (P < 0.05). There were no significant differences in all the indexes for heart (P > 0.05). CONCLUSIONS: The breast deformation during respiration may be disregarded in whole breast IMRT. PTV dose distribution is significantly changed between EI and EE phases, and the differentiation of the lung high dose area between EI and EE phases may be induced by thorax expansion. 3D treatment planning is sufficient for whole breast forward IMRT, but 4D CT scans assisted by respiratory gating ensures more precise delivery of radiation dose.