Masakazu Amari

Correlation of three-dimensional magnetic resonance imaging with precise histopathological map concerning carcinoma extension in the breast

This study was initiated to clarify the ability of magnetic resonance imaging (MRI) in defining breast carcinoma extension by comparing MRI to detailed histopathological analysis. Mastectomy (n=14) or quadrantectomy (n=44) specimens were sub-serially sectioned and mapped in detail in 58 breast cancer patients. Morphologically, we classified the lesions utilizing MRI into three patterns in relation to their histology. Numerically, we assessed the maximum distance of carcinoma extension using MRI, mammography, and ultrasonography (US). Linear regression was calculated for each of the three imaging measurements versus histopathological measurements.Three imaging patterns were observed by MRI, (1) localized (n=30), (2) segmentally extended (n=19), and (3) irregularly extended (n=5). The localized pattern showed a distinct focal mass, but in 10 cases, microscopic ductal carcinoma in situ (DCIS), or invasive lobular carcinoma, which were not depicted by MRI, existed. The segmentally extended pattern showed diffuse enhancement along duct–lobular segments, forming a ‘cone’ shape. Histologically, pure (n=4) or predominant (n=10) DCIS was distributed segmentally. The irregularly extended pattern showed thick branches extending out from the index tumor which were histologically revealed to be stromal invasion of ductal carcinoma. From the results of linear regressions, MRI was the most accurate modality in histologically measuring the extent of the cancer. When cases were limited to patients who were classified into segmentally or irregularly extended pattern by MRI (n=24), MRI was more accurate than mammography and US, even if they were combined (P<0.05).MRI may provide additional information concerning carcinoma extension prior to surgery, especially in patients classified into ‘extended patterns’ by MRI.

Comparison of core needle biopsy (CNB) and surgical specimens for accurate preoperative evaluation of ER, PgR and HER2 status of breast cancer patients

The roles of core needle biopsy (CNB) have become well established as an important preoperative diagnostic method for breast lesions. We examined the concordance of histological types, nuclear grades, hormone receptors, and human epidermal growth factor receptor 2 (HER2) status between CNB and surgical specimens in 353 cases. In addition, we analyzed the correlation between the number of CNB specimens obtained and accuracy of histological factors in order to explore the optimal number of CNB specimens. Between CNB and surgical specimens, concordance rates of histological type, nuclear grade, estrogen receptor (ER), and progesterone receptor (PgR) status (cut‐off 0–<1%, 1–10%, and 10%<), and HER2 were 84.4%, 81.3%, 92.9%, and 89.3%, respectively. In 52 of 353 patients who were histopathologically diagnosed as ductal carcinoma in situ (DCIS) by CNB, final diagnosis was changed in to invasive ductal carcinoma (IDC) in surgical specimens. Statistically significant differences were detected in the discrepancy of the following factors between CNB and subsequent surgical specimens: histological types, nuclear grade, and PgR, between patients who received four or more cores and those who had received three or less cores. In addition, a similar tendency was also detected in estrogen receptor (ER) and HER2 as in the above, and the cases that received four cores reached to 100% concordance in diagnosis between CNB and surgical specimens. Therefore, the optimal numbers of CNB were considered four at least in assessing the histological type, invasion, nuclear grade, hormone receptor status, and HER2 status of individual patients in the preoperative setting. (Cancer Sci 2010)

Age-specific interval breast cancers in Japan: estimation of the proper sensitivity of screening using a population-based cancer registry.

The age‐specific sensitivity of a screening program was investigated using a population‐based cancer registry as a source of false‐negative cancer cases. A population‐based screening program for breast cancer was run using either clinical breast examinations (CBE) alone or mammography combined with CBE in the Miyagi Prefecture from 1997 to 2002. Interval cancers were newly identified by linking the screening records to the population‐based cancer registry to estimate the number of false‐negative cases of screening program. Among 112 071 women screened by mammography combined with CBE, the number of detected cancers, false‐negative cases and the sensitivity were 289, 22 and 92.9%, respectively, based on the reports from participating municipalities. The number of newly found false‐negative cases and corrected sensitivity when using the registry were 34 and 83.8%, respectively. In detected cancers, the sensitivity of screening by mammography combined with CBE in women ranging from 40 to 49 years of age based on a population‐based cancer registry was much lower than that in women 50–59 and 60–69 years of age (40–49: 18, 71.4%, 50–59: 19, 85.8%, 60–69: 19, 87.2%). These data suggest that the accurate outcome of an evaluation of breast cancer screening must include the use of a population‐based cancer registry for detecting false‐negative cases. Screening by mammography combined with CBE may therefore not be sufficiently sensitive for women ranging from 40 to 49 years of age. (Cancer Sci 2008; 99: 2264–2267)

Correlation between mammographic findings and corresponding histopathology: Potential predictors for biological characteristics of breast diseases

The present study retrospectively evaluated the mammographic findings of 606 Japanese women with breast cancer (median age 50 years; range 27–89 years) and correlated them with histopathological characteristics. Mammographic findings were evaluated with an emphasis on mass shape, margin, density, calcification, and the presence of architectural distortion; these findings were correlated with histopathological characteristics such as intrinsic subtype, histological grade, lymphovascular invasion, and the Ki‐67 labeling index. An irregular mass shape and masses with a spiculated margin were significantly higher in the group of patients with luminal A breast cancer than in patients with masses that were lobular or round, or in tumors with an indistinct or microlobulated periphery (P = 0.017, P = 0.024, P < 0.001, and P = 0.001, respectively). Irregular mass shape and spiculated periphery were significantly lower in patients with Grade 3 cancer (P < 0.001 for both). In terms of lymphovascular invasion, there were significant differences between oval and irregular or round mass shape (P = 0.008 and P = 0.034), between tumors with a microlobulated and indistinct periphery (P = 0.014), between tumors with a punctate and amorphous or pleomorphic calcification shape (P = 0.030 and 0.038), and between the presence and absence of architectural distortion (P = 0.027). Equivalent or low‐density masses were also higher in Grade 1 breast cancers (P = 0.007). There were significant differences in the Ki‐67 labeling index between irregular and lobular or round tumors (P < 0.001 and P = 0.014), as well as between spiculated and indistinct or microlobulated tumors (P < 0.001 for both). Significant differences were noted in the mammographic features of different primary breast cancer subtypes. These proposed mammographic diagnostic criteria based on biological characteristics may contribute to a more accurate prediction of biological behavior of breast malignancies. (Cancer Sci 2011; 102: 2179–2185)

Hexokinase II in breast carcinoma: a potent prognostic factor associated with hypoxia-inducible factor-1α and Ki-67.

Hypoxia‐inducible factor‐1α (HIF‐1α) mediates adaptive responses to changes under tissue hypoxia in carcinoma cells by controlling the expression of various target genes. Previous studies have demonstrated that HIF‐1α is associated with adverse clinical outcome in breast carcinoma patients, but details of HIF‐1αs role have remained largely unknown. Therefore, in this study, we examined the expression profiles of HIF‐1α‐induced genes in 10 breast carcinoma cases using microarray data. As a result, we demonstrated that the status of hexokinase II (HKII) was associated with carcinoma recurrence in patients with these genes. The enzyme HKII is involved in the first, and rate‐limiting, step of glycolysis, but its clinical significance has not yet been examined in breast carcinoma. Therefore, we immunolocalized HKII in 118 breast carcinomas, and HKII immunoreactivity was detected in 44% of the cases. It is significantly associated with histological grade, Ki‐67 labeling index and HIF‐1α immunoreactivity. Also, HKII status is significantly associated with increased risk of recurrence and adverse clinical outcome in breast cancer patients. Subsequent multivariate analysis demonstrated that HKII status was an independent prognostic factor for disease‐free survival of patients. These results all suggest that HKII is induced by HIF‐1α and plays important roles in the proliferation and/or progression of breast carcinoma possibly through increased glycolytic activity. The status of HKII is therefore considered a potent prognostic factor in human breast cancer patients.

Effect of screening mammography on breast cancer survival in comparison to other detection methods: a retrospective cohort study.

The effectiveness of screening mammography (SMG) on mortality has been established in randomized controlled trials in Western countries, but not in Japan. This study evaluated the effectiveness by comparing the survival based on detection methods. The survivals were estimated by the Kaplan–Meier method. Breast cancer patients diagnosed from 1 January 1989 to 31 December 2000 were determined using the Miyagi Prefectural Cancer Registry and follow‐up was performed from the date of the diagnosis until the date of death or the end of follow‐up, 31 December 2005. The hazard ratios (HR) and 95% confidence interval (CI) of breast cancer death based on the detection methods were estimated by the Cox proportional‐hazard regression model. The mean age of the 7513 patients was 55.7 years (range, 15.0–99.3). The 5‐year survival associated with the SMG group, the clinical breast examination (CBE) group, and the self‐detection group was 98.3%, 94.3%, and 84.8%, respectively. The HR (95% CI) of deaths from breast cancer was 2.50 (1.10–5.69) for patients in the CBE group and 6.57 (2.94–14.64) for the self‐detection group in comparison to the SMG group. In women aged 50–59, the HRs were 1.64 (0.58–4.62) among the CBE group and 3.74 (1.39–10.03) among the self‐detection group, and the HRs for the CBE and self‐detection groups in women aged 60–69 were 2.96 (0.68–12.83) and 9.51 (2.36–38.26), respectively. After adjusting for stage, the HRs dropped remarkably. Screening mammography may be more effective in the elderly group and be able to reduce the mortality of breast cancer in Japan. (Cancer Sci 2009)

The Correlation Between Ultrasonographic Findings and Pathologic Features in Breast Disorders

OBJECTIVE Breast ultrasonography has gained widespread acceptance as a diagnostic tool for the evaluation of human breast disorders. It is important to evaluate the correlation of ultrasonography findings with the corresponding histopathological features. METHOD We retrospectively reviewed the 154 cases of breast disorders. We evaluated the correlation the ultrasonography findings and carcinoma cells extension with their corresponding histopathological findings. In addition, we also studied the information on estimation of histological types and cancer extension used by the other modalities such as computed tomography and magnetic resonance imaging. RESULTS The concordance rate for margins between ultrasonography findings and histopathological features was 91.6% (P < 0.001) and that for boundary zone was 87.0% (P < 0.001). Histopathological correlation of internal and posterior echoes demonstrated that internal low echo masses were composed of fibroblastic cells with marked collagenization in the stroma, or the cases in which carcinoma cells proliferated in a monotonous, solid and/or expanding manners. Attenuation of posterior echo was detected in the cases associated with hyperplasia of collagenized fibroblastic stroma. An increased cellularity in the mass with prominent large tumor nests and little fibrous stroma demonstrated the accentuation or no alterations of the posterior echo. The concordance rate of borders was 84.4% (P < 0.001). The correlation between estimated histological type by ultrasonography diagnosis and actual histological types was 87.0%. An overall detection rate of carcinoma extension by ultrasonography was 86.4%. In addition, an overall detection rate of carcinoma extension by ultrasonography, magnetic resonance imaging and computed tomography was 93.8%. CONCLUSION These results demonstrated correlation between histopathological and ultrasonographic findings of the breast lesions is cardinal for quality control or improving the quality of ultrasonography.

Retrospective analysis of mammographic findings for Japanese women: a potential predictor for breast malignancies.

This purpose of this study was to retrospectively stratify the risks of malignancy according to the mammographic characteristics of Japanese women. We studied the mammographic findings of 1267 Japanese women. We characterized malignant phenotypes according to mass shape, margin and mass density, and by shape and distribution of calcified foci, and to obtain possible predictors for malignancies according to age groups. Lobular and irregular mass shape, no circumscribed margin and higher density turned out to be more powerful predictors for malignancy than other radiological factors (P < 0.001, respectively). The ratio of the cases detected as a mass in those between 21 and 49 years was lower than that of other age groups. In addition, the presence of calcifications and no mammographic abnormalities were the most powerful predictors for malignancies in the young age groups (P < 0.001, respectively). The peak age of breast cancer is between 40 and 49 years in Japan. In the present study, subtle differences were found in the mammographic results for young and old women, in contrast to those of women in the USA and Europe. The results of this study might enable more accurate prediction of biological behavior of the breast lesions in Japanese women. (Cancer Sci 2012; 103: 472–476)

Breast Ultrasonographic and Histopathological Characteristics Without Any Mammographic Abnormalities

OBJECTIVE We evaluated ultrasonographic findings and the corresponding histopathological characteristics of breast cancer patients with Breast Imaging Reporting and Data System (BI-RADS) category 1 mammogram. METHODS We retrospectively reviewed the ultrasonographic findings and the corresponding histopathological features of 45 breast cancer patients with BI-RADS category 1 mammogram and 537 controls with mammographic abnormalities. We evaluated the ultrasonographic findings including mass shape, periphery, internal and posterior echo pattern, interruption of mammary borders and the distribution of low-echoic lesions, and the corresponding histopathological characteristics including histological classification, hormone receptor and human epidermal growth factor receptor 2 status of invasive ductal carcinoma and ductal carcinoma in situ, histological grade, mitotic counts and lymphovascular invasion in individual cases of BI-RADS category 1 mammograms and compared with those of the control group. RESULTS The ultrasonographic characteristics of the BI-RADS category 1 group were characterized by a higher ratio of round shape (P< 0.001), non-spiculated periphery (P= 0.021), non-interruption of mammary borders (P< 0.001) and non-attenuation (P= 0.011) compared with the control group. A total of 52.6% of low-echoic lesions were associated with spotted distribution in the BI-RADS 1 group, whereas 25.8% of low-echoic lesions were associated with spotted distribution in the control group (P= 0.012). As for histopathological characteristics, there was a statistically higher ratio of triple-negative subtype (P= 0.021), and this particular tendency was detected in histological grade 3 in the BI-RADS category 1 group (P= 0.094). CONCLUSION We evaluated ultrasonographic findings and the corresponding histopathological characteristics for BI-RADS category 1 mammograms and noted significant differences among these findings in this study. Evaluation of these ultrasonographic and histopathological characteristics may provide a more accurate ultrasonographic screening system for breast cancer in Japanese women.

Multidetector row helical computed tomography for invasive ductal carcinoma of the breast: correlation between radiological findings and the corresponding biological characteristics of patients.

The aim of this study is to evaluate the correlation between multidetector row helical computed tomography (MDCT) findings and the histopathological characteristics of patients with invasive ductal carcinoma. We retrospectively reviewed MDCT findings and the corresponding histopathological features of 442 women with invasive ductal carcinoma. We received informed consent from the patients and the protocol was approved by the Ethics Committee at Tohoku University. The median age was 53 years (26–89 years). We examined the MDCT findings based on mass shape classified into well, moderate, poorly and scattered demarcated shapes, the enhancement pattern classified into homogenous, heterogeneous, rim and poor, and mass density classified into high, intermediate or low. We subsequently compared these radiological findings with the histological characteristics and clinical outcome. Poorly demarcated types were higher in ER+/HER2− (P = 0.008), while the well‐demarcated type was higher in ER−/HER2− and ER−/HER2+ (P < 0.001 and P = 0.010). Rim pattern was higher in ER−/HER2− (P < 0.001). Intermediate or low density was higher in ER−/HER2− (P < 0.001, respectively). Further analysis based on histological grade, mitotic counts and lymphovascular invasion demonstrated that the well‐demarcated shape was higher in grade 2 and 3 (P = 0.006 and P < 0.001, respectively), and rim pattern was observed in grade 3 (P < 0.001). Regarding mitotic counts, poorly and scattered demarcated shapes were observed in score 1 (P = 0.008 and P = 0.014), while well‐demarcated shape and rim enhancement were observed in score 3 (P < 0.001, respectively). Lymphovascular invasion correlated with a moderate demarcated shape (P = 0.029). Regarding recurrence rates, there were statistically significant differences between well and moderate, poorly or scattered demarcated shapes (P = 0.007, 0.028 and 0.035, respectively). These proposed MDCT diagnostic criteria based on biological characteristics contribute to more accurately predicting the biological behavior of breast cancer patients. (Cancer Sci 2012; 103: 67–72)