| Objectives:The aim of this study was to evaluate whether there are correlations between the apparent diffusion coefficient (ADC) provided by 3.0T magnetic resonance diffusion-weighted imaging (DWI) and the prognostic factors of the breast invasive ductal carcinoma, including the histological grades, ER (estrogen receptor), PR (progesterone), HER-2 (human epidermal growth factor receptor-2), Ki-67 index, status of menstruation as well as metastasis of the lymph node. Also, to evaluate whether the ADC can predict the progress and the prognosis of the breast invasive ductal carcinoma.Materials and methods:A total of 48 female patients with completed clinical data at our institute were enrolled in this study. All had undergone 3.0T magnetic resonance imaging (MRI) of the breasts including DWI before operation, and surgery were done following the examination. The interval from MR examination to breast surgery were 4-7 days. All lesions were invasive ductal carcinoma confirmed by pathology. The age of the patients ranged from 27 to 63 years, with an average of (41.40±8.37) years. All patients did not have any clinical intervention (eg. hormone therapy, radiation therapy, surgery etc.) before MR examination. Of all the 48 patients,33 patients were done with breast-conserving surgery and 15 patients were done with a modified radical mastectomy.The images were acquired with a 3.0 Tesla (T) scanner (Magnetom verio, SIEMENS, Germany). All patients were examined in the prone position using a breast array coil. The MR images from the Verio scanner were acquired using the following sequences:1. axial, turbo spin-echo T2-weighted imaging sequence with a TR/TE of 3600/617; flip angle of 80°; 32 slices; FOV of 340 mm; matrix size of 314x320; 2 NEX; slice thickness of 4.0 mm; acquisition time of 2 minutes 47 seconds; 2. axial, fast low angle shot T1-weighted imaging sequence with a TR/TE of 600/13; flip angle of 20°; FOV of 340 mm; matrix size of 336×448; 1 NEX; slice thickness of 4.0 mm; acquisition time of 1 minute 44seconds; 3. axial DWI with echo planar imaging (EPI), with b of 0 and 1000 s/mm2; TR/TE of 2900/84; FOV of 230 mm; matrix size of 80×128; 4 NEX; slice thickness of 5.0 mm with a 1.5 mm slice gap, and acquisition time of 1 minutes 4 seconds; 4. T1-weighted dynamic three-dimensional fast low-angle shot sequence with TR/TE of 4.67/1.66; flip angle of 12°; FOV of 360 mm; matrix size of 296x384; 1 NEX; slice thickness of 1.2 mm with no gap; total scan 8 times; each scan time 60 s; 20s interval time between the first and the second scan; no interval time between the following scan; acquisition time of 9 minutes 16 seconds.Enhanced MR was performed by intravenously injecting 0.1mmol/kg～ 0.15mmol/kg Gd-DPTA (Godalinrum dithylene-triamine pentaacetic acid, Gd-DPTA. Hokuriku pharmaceutical company, China) at a rate of 2.5 ml/s, following 15 ml normal sodium reinjection at the same rate to make the best use of the diagnostic contrast agent. The injection of contrast agent was in the first two scan intervals.DWI was scanned before the dynamic enhanced MR in order to avoid the influence of the contrast. The slice center, the slice thickness, the field of view of the DWI were consistent with the axial of the T2WI. The region of the lesion was determined by two imaging experts according to the multi-parameters of the MR imaging. The ADC value of each lesion that underwent pathologic examination after operation was measured, and the ROI (region of interest) was placed on the solid portion of the lesion trying to avoid the cystic and necrosis portion.More than one ROIs were placed on a lesion when it was bigger. The mean ADC value of the lesion was calculated by averaging the ADC values of all voxels in all ROIs. The mean ADC values were acquired according to the following equation:where, n was the number of ROIs for a lesion; ADCi was the mean ADC value of the ith ROI; Si, was the area of the ith ROI. Because the areas of ROIs in a lesion often differed greatly, the area Si was as the weight of the ADCi; the equation can calculate the mean ADC accurately. Three groups of ROIs (n=3) were measured in this study.Tissues were stained with hematoxylin-eosin. The tumor was classified from grade Ⅰ to grade Ⅲ according to Elson-Ellis method. For tumor grading, tubule formation, pleomorphisms, and mitotic count were scored from 1 to 3 points. Cases in which the total score ranged from 3 to 5 were classified as grade Ⅰ. Cases in which the total score was 6 or 7 were classified as grade Ⅱ. Cases in which the total score was 8 or 9 were classified as grade Ⅲ. The grade Ⅰ and the grade Ⅱ was regarded as negative and the grade Ⅲ was regarded as positive. Metastasis of the tumor to a lymph node was considered by finding the carcinoma cells in the removed lymph node.ER, PR, HER-2, and the Ki-67 were regarded as a molecular prognostic marker. They were analyzed by using an immunohistochemical analysis of Elivision TM plus. ER, PR, Ki-67 were positioned in the cell nucleus and HER-2 in the cell membrane. The determination of whether ER, PR, Ki-67 positively expressed based on the percentile value (%) of stained cells. For ER and PR, tumors were deemed positive for hormone receptor if nuclear staining was observed greater than or equal to 1%of the tumor cells and negative if less than 1%. As for Ki-67, tumors were deemed positive for hormone receptor if nuclear staining was observed greater than or equal to 14% of the tumor cells and negative if less than 14%. The HER-2 expression was classified as 0,1+,2+or 3+ based on the standardized guidelines for primary breast cancer of 2011:0 for no membranous staining,1+ for weak uneven membranous staining in some of the tumor cells or less than 10% invasive tumor cells with weak to moderate membranous staining,2+for weak to moderate membranous staining in a large number of tumor cells (more than 10%) or less than 30% invasive tumor cells with distinctive membranous staining and 3+ for distinctive membranous staining in almost all of the tumor cells (more than 30%). Scores of 0 and 1+ were regarded as negative for over-expression of HER-2 protein, whereas scores of 2+ and 3+ were considered positive for over-expression of HER-2 protein. The status of axillary lymph node and the menstruation were also assessed.To examine whether the ADC value can provide prognostic information, the differences in ADC values of the different prognostic groups were analyzed. First, the clinical and histologic factors such as status of menstruation, axillary lymph node metastasis and tumor grades were compared with ADC values using the independent sample t-test. And then, in cases in which the prognostic factors(ER、PR、Ki-67、HER-2) were classified as the positive group and the negative group, the independent sample t-test was used as well. Pearson correlation coefficients (r values) were calculated to quantify the correlation between ER, PR and ADC values whereas Spearman correlation coefficients to quantify the correlation between Ki-67, HER-2 and ADC values. All the statistical analyses were performed using statistical software (SPSS, version 17), and a value of P<0.05 was considered significant.Results:Forty-eight lesions in 48 patients were determined as the invasive dutal carcinoma according to the histologic results. The largest one of the lesions was about 4cm×3 cm and most of the others (44/48,91.7%) were less than or equal to 2.5cm in diameter. The characteristics of the lesions were as followings:histologic grades Ⅰ/Ⅱ (less aggressive group) in 31 (31/48,64.6%), grade Ⅲ (more aggressive group) in 17 (17/48,35.4%); postmenopausal patients in 7 (7/48,14.6%); lymph node metastasis in 11 (11/48,22.9%); positive expression of ER in 31 (31/48,64.6%), PR in 32 (32/48, 66.7%), HER-2 in 26 (26/48,54.1%) and Ki-67 in 30 (30/48,62.5%).The tumor grade reflecting mitosis showed that the median ADC values of grade Ⅰ/Ⅱ and grade Ⅲ were (1.105±0.229)×10-3mm2/s and (0.925±0.150)×10-3mm2/s respectively. The statistical result using the independent sample t-test showed that the ADC value was lower in grade Ⅲ than in grade Ⅰ/Ⅱ tumors, and there was a statistical significance between grade Ⅲ and grade Ⅰ/Ⅱ tumors (P=0.006). The mean ADC value of postmenopausal group was (1.039±0.196)×10-3mm2/s and premenopausal group was (1.042±0.227)×10-3mm2/s, there was no statistical significance between the two groups (P=0.969); The mean ADC value of which with axillary lymph node metastasis group was (0.991±0.112)×10-3mm2/s and without axillary lymph node metastasis group was (1.057±0.243)×10-3mm2/s and the statistical result showed the former was slightly lower than the latter (P=0.215).The mean ADC value of ER-positive cancer was (0.988±0.184)×10-3mm2/s, and it was significantly lower than that of ER-negative group of (1.140±0.253) ×10-3mm2/s. The statistical result using the independent sample t-test showed there was a statistical significance between the two groups (P=0.021). The mean ADC value of PR-positive cancer (0.960±0.155)×10-3mm2/s was significantly lower than that of PR-negative (1.204±0.246)×10-3mm2/s, and there was a statistical significance between the two groups (P=0.000). The mean ADC value of Ki-67 index-positive cancer (0.987±0.222)×10-3mm2/s was significantly lower than that of Ki-67 index-negative cancer (1.148±0.196)×10-3mm2/s, and there was a statistical significance between the two groups (P=0.019) as well. The mean ADC value of HER-2-positive cancer and HER-2-negative cancer was (1.096±0.260)×10-3mm2/s and (1.000±0.260)×10-3mm2/s respectively, there was no statistical significance between the HER-2-positive group and HER-2-negative group (P=0.120).The Pearson correlation analysis showed a statistically significant (Pearson coefficient r=—0.335, P=0.020) negative correlation was disclosed between the ADC value and the ER; a statistically significant (Pearson coefficient r=—0.495, P= 0.000) negative correlation was disclosed between the ADC value and the PR. The Spearman correlation coefficient showed that there was a certain linear relationship between the Ki-67 index and the ADC values (Spearman coefficient r=—0.299, P =0.043). But there was no statistical significance correlation between the ADC value and the HER-2 (Spearman coefficient r=—0.146, P=0.321).Conclusion:The mean ADC value of the grade Ⅰ/Ⅱ invasive ductal carcinoma was higher than that of grade Ⅲ, that is to say, the higher of the histological grade, the greater of the malignancy degree, and the lower of the ADC values of the tumor. There were significant negative correlations between the ADC values and molecular prognostic factors, including ER, PR and the Ki-67 index. The ADC values of the positive groups of the ER, PR and the Ki-67 index were significant lower than those of negative groups. Although there were no significant correlations between the ADC values and classical prognostic factors including menstrual status and the lymph node metastasis, menstrual status could be definited by asking medical history and the lymph node metastasis could be found by physical examination or on routine MRI sequence. So we believe that as a noninvasive examination technology, the DWI of the breast can provide some useful information about the preoperative evaluation, the formulation of treatment, predict prognosis from the histology and the molecular biology, and can provide a simple, easy and noninvasive examination methods for the patients of the breast cancer. |
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