Male accessory breast cancer on the abdominal wall: a case report and literature review.

BACKGROUND: Accessory breast cancer is very rare, particularly in men. Male accessory breast cancer on the abdominal wall has not been documented in the scientific literature so far. We describe a case of male accessory breast cancer on the abdominal wall. CASE PRESENTATION: We describe a male patient suffering a swelling and erosive, enlarged, and hardened abdominal wall mass with pain due to abdominal wall accessory breast cancer. The patient had no obvious disease history, and the initial clinical symptom was a small mass on the abdominal wall. B-ultrasound revealed a solid subcutaneous nodule in the right abdomen with a size of ~2.8 × 2.5 × 1.5 cm. The abdominal wall tumor resection was performed with local anesthesia. Pathological testing revealed a grade II infiltrating ductal carcinoma derived from the accessory mammary gland (right abdominal wall) with neuroendocrine characteristics, showing ER (100% strong positive), PR (100% strong positive), HER-2 (-), ki67 (40% positive), Syn (+), CgA (+), and GCDFP15 (+). CONCLUSION: Nonaxillary accessory breast cancer in males is very rare, with no obvious clinical manifestations, and could be easily ignored. This disease requires great attention from clinicians.

Clinicopathologic Factors Related to the Histological Tumor Grade of Breast Cancer in Western China: An Epidemiological Multicenter Study of 8619 Female Patients.

BACKGROUND AND PURPOSE: Breast cancer is now recognized as a clinically heterogeneous disease with a wide spectrum of epidemiological and clinicopathologic features. We aimed to evaluate whether epidemiological and clinicopathologic features are associated with the histological tumor grade of breast carcinomas in Western China. METHODS: We retrospectively collected data from the Western China Clinical Cooperation Group and assessed associations between clinicopathologic factors and histological tumor grade in 8619 female breast cancer patients. Patients were divided into two groups: Group I (tumor grade I/II) and Group II (tumor grade III). Univariable analysis and multivariable logistic regression models were used to analyze the relationships between clinicopathologic factors and tumor grade. RESULTS: Patients presenting with positive axillary lymph nodes, large tumor size (>2 cm), lymphovascular invasion, hormone receptor negativity, human epidermal growth factor receptor 2 (HER-2) positivity, and triple negativity tended to have an increased risk of a high tumor grade. However, the number of pregnancies or births was inversely correlated with the risk of a high tumor grade. In addition, patients presenting with grade III tumors were more likely to receive aggressive treatment, such as adjuvant chemotherapy, anti-HER-2 therapy, and level III axillary lymph node dissection. CONCLUSIONS: Our results suggested that several clinicopathologic factors were associated with high tumor grade of breast cancer patients in Western China.

Relationship between mammographic calcifications and the clinicopathologic characteristics of breast cancer in Western China: a retrospective multi-center study of 7317 female patients.

BACKGROUND AND PURPOSE: Limited information is available regarding the correlations between mammographic calcifications and the epidemiological features of patients with breast cancer living different lifestyles in Western China. Thus, this study aimed to investigate the relationship between mammographic calcifications and the epidemiological characteristics of female patients with breast cancer in Western China. METHODS: This was a hospital-based, retrospective, multi-center epidemiological study of patients with breast cancer. Using the Western China Clinical Cooperation Group (WCCCG) database, we obtained the records of 7317 patients (with mammographic data) diagnosed with breast cancer between March 2011 and June 2016. These patients were divided into Groups I (mass alone) and II (mass combined with calcification), and their clinical and pathological data were compared. RESULTS: A total of 4211 patients were enrolled in Group I, and 3106 patients were enrolled in Group II. The tumors in Group II were more likely to be larger (P < 0.0001), higher grade (P = 0.0029), estrogen receptor (ER)+/progesterone receptor (PR)- (P = 0.0319), and human epidermal growth factor receptor 2 (HER-2)-positive (P < 0.0001), and to have axillary lymph node metastasis (P = 0.0033) than those in Group I. Regarding treatment, patients in Group II were more likely to have undergone chemotherapy (P = 0.0108) and anti-HER2 therapy (P = 0.0102), whereas patients in Group I were more likely to have undergone endocrine therapy (P < 0.0001). CONCLUSIONS: In conclusion, mammographic calcifications in tumors were associated with distinct clinicopathologic characteristics and aggressive treatments.

RSK4 knockdown promotes proliferation, migration and metastasis of human breast adenocarcinoma cells.

RSK4 has been shown to inhibit the growth of certain cancer cells. The aim of this study was to construct a lentiviral vector of RSK4-shRNA (Lenti-RSK4-shRNA) to specifically block the expression of RSK4 in the human breast adenocarcinoma cell line MCF-7, and investigate the effect of the RSK4 gene on cell proliferation and invasion in vitro and in vivo. Lenti-RSK4-shRNA was stably transfected into MCF-7 cells. RSK4 mRNA and protein expression were measured by fluorescence quantitative RT-PCR and western blot analysis. Cell proliferation was evaluated by MTT assays and flow cytometric analysis. Invasion was evaluated by Transwell assays and xenograft nude mouse models. The expression of RSK4 mRNA, Ki-67 mRNA, cyclin D1 mRNA, CXCR4 mRNA and E-cadherin mRNA of tumor xenografts were detected by fluorescence quantitative RT-PCR. Significant decreases in RSK4 mRNA and protein expression was detected in MCF-7 cells carrying lentiviral RSK4-shRNA vector. The cell proliferation was significantly promoted in the RSK4-shRNA group as compared to that in the negative and blank control group. In addition, the number of cells in the S phase in the RSK4­shRNA group was significantly greater than the blank and negative control groups (P<0.05). Furthermore, the number of invading cells was increased in the RSK4-shRNA (P<0.05). In vivo, we also found that the knockdown of RSK4 promoted tumorigenicity and migration in the xenograft nude mouse model. In addition, we showed that the RSK4 mRNA and E-cadherin mRNA expression were significantly lower in the RSK4-shRNA group compared to that in negative and blank control group (both P<0.05), while the Ki-67 mRNA, cyclin D1 mRNA and CXCR4 mRNA were higher in the shRNA group compared to that in negative and blank control group (both P<0.05). In conclusion, downregulation of RSK4 expression is indicated to be associated with tumor cell proliferation and invasion, and silencing of the RSK4 may be involved in the development and progression of breast cancer through the changes of Ki-67, cyclin D1, CXCR4 and E-cadherin, and suggesting that RSK4 may act as a potential cancer suppressor gene and therapeutic target for the treatment of breast cancer.

Clinical usefulness of breast-specific gamma imaging as an adjunct modality to mammography for diagnosis of breast cancer: a systemic review and meta-analysis.

PURPOSE: The purpose of this study was to assess the diagnostic performance of breast-specific gamma imaging (BSGI) as an adjunct modality to mammography for detecting breast cancer. METHODS: Comprehensive searches of MEDLINE (1984 to August 2012) and EMBASE (1994 to August 2012) were performed. A summary receiver operating characteristic curve (SROC) was constructed to summarize the overall test performance of BSGI. The sensitivities for detecting subcentimetre cancer and ductal carcinoma in situ (DCIS) were pooled. The potential of BSGI to complement mammography was also evaluated by identifying mammography-occult breast cancer. RESULTS: Analysis of the studies revealed that the overall validity estimates of BSGI in detecting breast cancer were as follows: sensitivity 95 % (95 % CI 93-96 %), specificity 80 % (95 % CI 78-82 %), positive likelihood ratio 4.63 (95 % CI 3.13-6.85), negative likelihood ratio 0.08 (95 % CI 0.05-0.14), and diagnostic odds ratio 56.67 (95 % CI 26.68-120.34). The area under the SROC was 0.9552 and the Q* point was 0.8977. The pooled sensitivities for detecting subcentimetre cancer and DCIS were 84 % (95 % CI 80-88 %) and 88 % (95 % CI 81-92 %), respectively. Among patients with normal mammography, 4 % were diagnosed with breast cancer by BSGI, and among those with mammography suggestive of malignancy or new biopsy-proven breast cancer, 6 % were diagnosed with additional cancers in the breast by BSGI. CONCLUSION: BSGI had a high diagnostic performance as an excellent adjunct modality to mammography for detecting breast cancer. The ability to identify subcentimetre cancer and DCIS was also high.

[Effects of breast cancer cells stably overexpressing RSK4 on growth of transplanted human breast cancer in severe combined immunodeficiency mice].

OBJECTIVE: To construct a breast cancer cell line MD-MB-231 stably overexpressing RSK4 gene and study its in vivo effects on tumor tumorigenesis. METHODS: The MD-MB-231 cells were transfected with pcDNA3.1/Neo and pcDNA3.1/Neo-RSK4 by lipofectamin transfection respectively. The stable expression of RSK4 (MR11 and MR12) and control vector (MN10 and MN11) were inoculated into severe combined immunodeficiency (SCID) mice subcutis to establish a model of human breast cancer in SCID mice. The xenograft tumor growth, invasion and metastasis were observed after 6 - 10 weeks. RESULTS: The stable cell lines MR11, MR12 and MN10, MN11 were screened successfully. We constructed the human breast cancer transplanted model and dissected SCID mice. After 6 weeks, SCID mice subcutis of the MN10/MN11 group yielded 10/10 metastatic tumors versus 6/10 and 7/10 in the MR11/MR12 group respectively. MR11 and MR12 showed much smaller tumor sizes and significantly reduced tumor volume and weight versus MN10 and MN11 (P < 0.001). In the control group, visceral metastasis developed in 80% (8/10) of mice while in metastasis developed in 40% (4/10) of mice injected with RSK4-overexpressing MDA-MB-231 cells. Histological examination of hematoxylin and eosin-stained paraffin sections of lungs revealed numerous metastases in mice injected with vector control cells whereas RSK4-overexpressing cells showed markedly decreased metastatic lesions. CONCLUSION: Transplanted human breast cancer in SCID mice closely correlates with the disease course of clinical tumor patients. Overexpression of RSK4 can inhibit tumor growth of transplanted human breast cancer in SCID mice.

Silencing of lysyl oxidase gene expression by RNA interference suppresses metastasis of breast cancer.

OBJECTIVE: The aim of this study was to investigate possible mechanisms of LOX gene effects on invasion and metastasis of breast cancer cells by RNA interference. METHODS: LOX-RNAi-LV was designed, synthesized, and then transfected into a breast cancer cell line (MDA-MB-231). Expression of LOX, MMP-2 and MMP-9 was determined by real-time PCR, and protein expression of LOX by Western blotting. Cell migration and invasiveness were assessed with Transwell chambers. A total of 111 cases of breast cancer tissues, cancer-adjacent normal breast tissues, and 20 cases of benign lesion tissues were assessed by immunohistochemistry. RESULTS: Expression of LOX mRNA and protein was suppressed, and the expression of MMP-2 and MMP-9 was significantly lower in the RNAi group than the control group (P<0.05), after LOX-RNAi-LV was transfection into MDA-MB-231 cells. Migration and invasion abilities were obviously inhibited. The expression of LOX protein in breast cancer, cancer-adjacent normal breast tissues and benign breast tumor were 48.6% (54/111), 26.1% (29/111), 20.0% (4/20), respectively, associations being noted with clinical stage, lymph node metastasis, tumor size and ER, PR, HER2, but not age. LOX protein was positively correlated with MMP-2 and MMP-9. CONCLUSION: LOX displayed an important role in invasion and metastasis of breast cancer by regulating MMP-2 and MMP-9 expression which probably exerted synergistic effects on the extracellular matrix (ECM).

[Mechanism of lysyl oxidase (LOX) in breast cancer invasion and metastasis].

OBJECTIVE: To investigate possible mechanism of silencing lysyl oxidase (LOX) gene by RNA interference affecting on invasion and metastasis of breast cancer cells. METHODS: LOX-RNAi-LV was designed and synthesized, which was transfected into breast cancer cell line MDA-MB-231. The expressions of LOX, MMP-2 and MMP-9 were determined by Real-time PCR in MDA-MB-231 cells, and the protein expression of LOX was determined by Western blot. The cells migration and invasion abilities were measured by cell migration and invasion test. 111 cases of breast cancer tissue and cancer-adjacent breast tissues and 20 cases of benign lesion tissues of LOX, MMP-2 and MMP-9 were detected by immunohistochemistry, and the relationship of LOX and clinicopathological characteristics was analyzed. RESULTS: The expression levels of LOX mRNA and protein were down-regulated obviously after transfecting LOX-RNAi-LV, with the inhibition rate 89.2% ± 1.3% and 84.4% ± 0.4% respectively. The relative expressions of MMP-2 and MMP-9 mRNA were 0.496 ± 0.021 and 0.571 ± 0.099 in RNAi group, which was significantly lower than that in negative control group (0.846 ± 0.047, 0.786 ± 0.042) and blank control group (1.000 ± 0.000, 1.000 ± 0.000) (both P < 0.05). Cell migration and invasion test showed the average cell numbers per field in the group RNAi were 47 ± 2 and 63 ± 2, was significantly lower than that in negative control group (100 ± 1, 118 ± 2) and blank control group (100 ± 1, 118 ± 2) (both P < 0.05). The expression of LOX protein in breast cancer, cancer-adjacent breast tissues and benign breast tumor were 48.6% (54/111), 26.1% (29/111), 20.0% (4/20), the expression of LOX protein in breast cancer was significantly higher than that in cancer-adjacent breast tissues and benign lesion tissues (P = 0.019). The expression of LOX protein was associated with clinical stage, lymph node metastasis, tumor size. Correlation analysis showed that LOX protein expression was significantly positive correlation with MMP-2 (r = 0.262, P = 0.005) and MMP-9 (r = 0.424, P = 0.000). CONCLUSION: LOX can promote invasion and metastasis of breast cancer; LOX and MMP-2, MMP-9 may have a synergistic role in promoting invasion and metastasis of breast cancer.

Diagnostic value of fine-needle aspiration biopsy for breast mass: a systematic review and meta-analysis.

BACKGROUND: Fine-needle aspiration biopsy (FNAB) of the breast is a minimally invasive yet maximally diagnostic method. However, the clinical use of FNAB has been questioned. The purpose of our study was to establish the overall value of FNAC in the diagnosis of breast lesions. METHODS: After a review and quality assessment of 46 studies, sensitivity, specificity and other measures of accuracy of FNAB for evaluating breast lesions were pooled using random-effects models. Summary receiver operating characteristic curves were used to summarize overall accuracy. The sensitivity and specificity for the studies data (included unsatisfactory samples) and underestimation rate of unsatisfactory samples were also calculated. RESULTS: The summary estimates for FNAB in diagnosis of breast carcinoma were as follows (unsatisfactory samples was temporarily exluded): sensitivity, 0.927 (95% confidence interval [CI], 0.921 to 0.933); specificity, 0.948 (95% CI, 0.943 to 0.952); positive likelihood ratio, 25.72 (95% CI, 17.35 to 28.13); negative likelihood ratio, 0.08 (95% CI, 0.06 to 0.11); diagnostic odds ratio, 429.73 (95% CI, 241.75 to 763.87); The pooled sensitivity and specificity for 11 studies, which reported unsatisfactory samples (unsatisfactory samples was considered to be positive in this classification) were 0.920 (95% CI, 0.906 to 0.933) and 0.768 (95% CI, 0.751 to 0.784) respectively. The pooled proportion of unsatisfactory samples that were subsequently upgraded to various grade cancers was 27.5% (95% CI, 0.221 to 0.296). CONCLUSIONS: FNAB is an accurate biopsy for evaluating breast malignancy if rigorous criteria are used. With regard to unsatisfactory samples, futher invasive procedures are required in order to minimize the chance of a missed diagnosis of breast cancer.

[Abnormal expression of RSK-4 and its clinical significance in breast cancer].

OBJECTIVE: To study the expression and clinical significance of ribosomal S6 kinase-4 (RSK-4) in breast cancer and explore the role of RSK-4 in the genesis and development of breast cancer. METHOD: The expression levels of RSK-4 mRNA and protein were detected in 56 cases of breast cancer and the normal breast tissues, as well as in 20 cases of breast benign lesions, by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: The expression rates of RSK-4 mRNA in breast cancer, the normal breast tissues and breast benign lesions were 48.2%, 76.8% and 75.0%, respectively. The expression level of RSK-4 mRNA in breast cancer was significantly lower than those in normal breast tissues and breast benign lesions tissues (P < 0.05). The expression level of RSK-4 significantly correlated with tumor size and clinical stage (P < 0.05).The expression rate of RSK-4 protein was 39.3% in breast cancer tissues, which was significantly lower than that of normal breast tissues (71.4%) and breast benign lesions (75.0%, P < 0.01). The expression level of RSK-4 protein was lower in breast cancer with large tumor, high clinical stage and lymph node metastasis. In 56 cases of breast cancer samples, the consistency rate of RSK-4 mRNA and protein was 73.2%. A significant correlation was found between RSK-4 mRNA and protein (χ² = 10.254, P < 0.05). CONCLUSION: The down-regulation of RSK-4 expression in breast caner suggests that it is a breast cancer suppressor gene, and the lack or down-regulation of RSK-4 expression is involved in the genesis and progression of breast cancer.

Telomerase activity and human telomerase reverse transcriptase expression in colorectal carcinoma.

AIM: To study the activity of telomerase and the expression of human telomerase reverse transcriptase (hTERT) in colorectal carcinoma and its adjacent tissues, normal mucosa and adenomatoid polyp, and to evaluate their relation with carcinogenesis and progression of colorectal carcinoma. METHODS: Telomerase activity and hTERT expression were determined in 30 samples of colorectal carcinoma and its adjacent tissues, normal mucosa and 20 samples of adenomatoid polyp by modified telomeric repeat amplification protocol (TRAP), enzyme-linked immunosorbent assay (ELISA) and immunohistochemical method. RESULTS: Telomerase activity and hTERT expression were 83.33% (25/30) and 76.67% (23/30) respectively in colorectal carcinoma, which were obviously higher than those in paracancerous tissues (13.33%, 16.67%), normal mucosa (3.33%, 3.33%) and adenomatoid polyp (10%, 10%). There was a significant difference between colorectal carcinoma and other tissues (P=0.027). The telomerase activity and hTERT expression were higher in colorectal carcinoma with lymphatic metastasis than in that without lymphatic metastasis (P=0.034). When the histological classification and clinical stage were greater, the telomerase activity and hTERT expression increased, but there was no significant difference between them. In colorectal carcinoma, the telomerase activity was correlated with hTERT expression (positive vs negative expression of telomerase activity and hTERT, P=0.021). CONCLUSION: Telomerase activity is closely correlated with the occurrence, development and metastasis of colorectal carcinoma. Overexpression of hTERT may play a critical role in the regulation of telomerase activity.

[Expression of small breast epithelial mucin mRNA in peripheral blood of breast cancer patients and its clinical significance].

BACKGROUND & OBJECTIVE: The major cause of death in breast cancer patients is distant metastasis. This study was to explore the expression and significance of small breast epithelial mucin (SBEM) mRNA, the specific marker of breast cancer, in peripheral blood of breast cancer patients. METHODS: Expression of SBEM mRNA in peripheral blood samples from 67 breast cancer patients, 16 benign breast disease patients, and 20 healthy volunteers was detected by nested reverse transcription-polymerase chain reaction (nested RT-PCR). RESULTS: SBEM mRNA was not detected in healthy volunteers and benign breast disease patients. Positive rate of SBEM mRNA was 50.7% (34/67) in breast cancer patients. Positive rate of SBEM mRNA was 25.0% (2/8) in stage I patients, 45.8% (11/24) in stage II patients, 43.8% (7/16) in stage III patients, and 73.7% (14/19) in stage IV patients, respectively. Positive rate of SBEM mRNA was significantly higher in stage IV patients than in stages I, II, and III patients (P0.05). The expression of SBEM mRNA in peripheral blood was not correlated with patient's age, primary tumor size, pathologic type, and estrogen or progestin receptor status (P0.05). CONCLUSION: SBEM mRNA is specifically expressed in peripheral blood of breast cancer patients, and may be a marker of micrometastasis of breast cancer.