c-erbB-2在乳腺癌组织中的表达及其与ER、PR和临床病理的关系

目的 探讨癌基因ｃｅｒｂ Ｂ２ 在乳腺癌组织中的表达，和与雌激素受体 Ｅ Ｒ、孕激素受体 Ｐ Ｒ 的关系，及其与临床病理的关系。方法 应用免疫组织化学 Ｓ Ｐ 法检测６１ 例乳腺癌手术切除组织中ｃｅｒｂ Ｂ２ 、 Ｅ Ｒ、 Ｐ Ｒ 的表达。结果 ｃｅｒｂ Ｂ２ 、 Ｅ Ｒ、 Ｐ Ｒ在乳腺癌中的表达阳性率分别为４０ ．９８ ％ 、７８ ．７５ ％ 、８１ ．９ ％ 。ｃｅｒｂ Ｂ２ 表达：在 Ｅ Ｒ Ｐ Ｒ 阴性高于 Ｅ Ｒ Ｐ Ｒ 阳性组（ Ｐ＜ ０ ．０５） 在淋巴结转移组的乳腺癌高于淋巴结未转移组（ Ｐ＜ ０ ．０５） 并随组织学分级增高。结论 ｃｅｒｂ Ｂ２ 与 Ｅ Ｒ、 Ｐ Ｒ 及临床病理结合有利于临床预测乳腺癌恶性程度及预后。

Ki-67 as a prognostic marker according to breast cancer molecular subtype

Objective: Ki-67 plays an important function in cell division, but its exact role is still unknown. Moreover, few works regarding its overall function were published. The present study evaluated the clinical significance of Ki-67 index as a prognostic marker and predictor of recurrence in different molecular subtypes of breast cancer. The relationship of Ki-67 index with different clinicopathological factors was also analyzed.Methods: Ki-67 index was measured in 107 cases of primary breast cancer from 2010-2012. These patients were evaluated for estrogen receptor, progesterone receptor, and HER2. Ki-67 was divided according to percentage levels: < 15% and > 15%. Followup ranged from 32 months up to 6 years.Results: Approximately 44, 23, 15, and 25 cases were grouped as luminal A, luminal B, HER2 subtype, and triple-negative(TN),respectively. No luminal A patients showed Ki-67 level higher than 15%, and their recurrence was 20%. In luminal B group, Ki-67 level higher than 15% was observed in 69% of patients, and recurrence was 39%. In HER2 subtype, Ki-67 was higher than 15% in34% of cases, and recurrence was 40%. In triple-negative cases, Ki-67 was higher than 15% in 60% of cases, and recurrence was detected in 32% of patients. Patients with Ki-67 less than 15% displayed better overall survival than those with Ki-67 higher than15%(P = 0.01). Patients with Ki-67 higher than 15% exhibited higher incidence of metastasis and recurrence than those with Ki-67 less than 15%(P = 0.000).Conclusions: Ki-67 may be considered as a valuable biomarker in breast cancer patients.

Treatment for triple-negative breast cancer

Triple-negative breast cancers (TNBCs) neither express estrogen receptor and progesterone receptor nor over- express human epidermal growth factor receptor-2. Because of the special molecular features, triple-negative breast cancer is not either sensitive to endocrine therapy or targeted therapy of trastuzumab. There has not been standard treatment regimen for triple-negative breast cancer yet and chemotherapy has still been the chief therapy currently. However, with the great progress of oncology and molecular biology, the understanding of the natural history, pathophysiology and molecular features of this disease has been greatly improved, and a growing number of novel and effective therapies and discoveries of new biological targets for this phenotype of breast cancers have been reported, which provide new insights into therapeutic strategies for the women suffering from it.

Clinico-pathological significance of extra-nodal spread in special types of breast cancer

Objective: To investigate the significance of extra-nodal spread in special histological sub-types of breast cancer and the relationship of such spread with prognostic parameters.Methods: A total of 303 breast cancer cases were classified according to tumor type, and each tumor group was subdivided according to age, tumor diameter, lymph node metastasis, extra-nodal spread, vein invasion in the adjacent soft tissue, distant metastasis, and immunohistochemical characteristics [estrogen receptor(ER), progesterone receptor(PR) existence, p53, c-erbB-2, and proliferative rate(Ki-67)]. The 122 cases with extra-nodal spread were clinically followed up.Results: An extra-nodal spread was observed in 40%(122 cases) of the 303 breast cancer cases. The spread most frequently presented in micro papillary carcinoma histological sub-type(40 cases, 75%), but least frequently presents in mucinous carcinoma(2 cases, 8%). Patients with extra-nodal spread had a high average number of metastatic lymph nodes(8.3) and a high distant metastasis rate(38 cases, 31%) compared with patients without extra-nodal spread.Conclusion: The existence of extra-nodal spread in the examined breast cancer sub-types has predictive value in forecasting the number of metastatic lymph nodes and the disease prognosis.

Effects of Fuke Qianjin Formula on hormones and their receptors and metabonomics study in uterine fibroids model rats

Objective To investigate the effects of different fractions from Fuke Qianjin Formula(妇科千金方,FKQJF)on uterine leiomyoma(UL)to determine the best fraction.Methods FKQJF was extracted and isolated to obtain polysaccharides(FKP),flavonoids(FKF),and grease(FKG).140 female SPF SD rats were divided into 14 groups[model(MOD),normal control(NC),Gouliuqing(GLQ),Mifepristone(MFST),FKQJF,low,medium,and high dose of polysaccharides(l-FKP,m-FKP,and h-FKP),low,medium,and high dose of flavonoids(l-FKF,m-FKF,and h-FKF),low,medium,and high dose of grease(l-FKG,m-FKG,and h-FKG)],and uterine fibroids model rats were treated with drugs for four weeks.Serum levels of estrogen and progesterone were measured using enzyme-linked immunoassay assay(ELISA)kits.The expression of estrogen receptor(ER-α,ER-β)and progesterone receptor(PR)in the uterus was observed using immunohistochemistry(IHC).Serum metabolite profiles and FKG were analyzed using gas chromatography-mass spectrometry(GC-MS).Results FKQJF,h-FKF,m-FKG,and h-FKG significantly downregulated the estrogen level in the uterine fibroid model rats(P<0.01).FKQJF,h-FKF,and h-FKG significantly reduced the level of progesterone in the uterine fibroid model rats(P<0.01).The levels of ER-α,ER-β,and PR in uterine fibroid model rats were significantly decreased by FKQJF and h-FKG(P<0.01).The levels of ER-α,ER-β,and PR in the fibroid model rats were decreased by m-FKG(P<0.05).Additionally,serum metabolism results revealed that h-FKG and FKQJF could regulate related endogenous metabolites and make the pathological indices of uterine fibroids in rats close to the normal group.Forty-six components were identified in the oil,accounting for 91.97%of the total oil components.Conclusion FKQJF and h-FKG showed a significant anti-myoma activity and significantly improved the pathological state of the uterus in rats with hysteromyoma.The mechanism of action may be related to the regulation of estrogen progesterone and its receptor in uterine fibroid model animals.These findings proved the effect of FKQJF on uterine leiomyoma and provided an experimental basis for its clinical research and application.

Genomic structure analysis of SNC6, a progesterone-receptor associated protein gene, and cloning and characterization of its 5＇-flanking region

Objective: To analyze the genomic structure of SNC6, a progesterone\|receptor associated protein gene and its regulatory elements in its 5'\|flanking region. Methods: Genomic sequence from GenBank database (accession number: Z98048) covering the whole SNC6 gene was used to analyze the genomic structure of SNC6 and design primers for PCR amplification of its 5'\|flanking region. A 1894 bp fragment of the 5'\|flanking region \{(-1814\} to +75) was cloned by PCR using genomic DNA from a healthy donor peripheral blood lymphocyte as template. This fragment, as well as 3 shorter derivative fragments (1423 bp, 632 bp and 416 bp, which correspond to -1344 to +75, -552 to +75 and -337 to +75 respectively), were subcloned into pGL2 series luciferase reporter vectors. These constructs were introduced into colorectal cancer cell line SW620 for transient expression of reporter gene and luciferase activities were measured. Results: The genomic structure analysis showed there are 12 exons for SNC6 gene, which spans 32017 bp (nt71529 to nt39513 in Z98048 sequence). All transfected SW620 cells with the above 5\|flanking region\|containing constructs showed luciferase activities. The highest luciferase activities were measured in transfected cells with vectors containing 1894 bp fragments, and the lowest luciferase activities were measured in transfected cells with vectors containing 416 bp fragments. Luciferase activities were higher in transfected cells with vectors containing 632 bp fragments than that in transfected cells with vectors containing 1423 bp fragments. Conclusion: The basic transcription\|promoting element (promoter) for SNC6 expression resides between 0 to -337, and two transcription\|enhancing elements (enhancer) resides between -337 to -552 and -1344 to -1814, whereas one transcription\|inhibiting element (silencer) exists between -552 to -1344.

Relationship between expression of ER, PR, Her-2, Ki-67 and neoadjuvant chemotherapy effect in breast cancer

Objective: The purpose of the study was to investigate the relationship between the expression of estrogen receptor(ER), progestogen receptor(PR), human epidermal growth factor receptor(Her-2), Ki-67 and the effect of neoadjuvant chemotherapy in breast cancer. Methods: The expression of ER, PR, Her-2 and Ki-67 in 45 breast cancers which received neoadjuvant chemotherapy was detected by immunohistochemistry. Results: The effective rates in ER negative and PR negative groups were higher than those in ER positive and PR positive groups(83.3% vs 59. 4%, 82.4% vs 60.6%). There was no significant difference of the effective rate between Her-2 overexpressed group and Her-2 non-overexpressed group(81.8% vs 64.1%), and the same thing happened between Ki-67 negative group and Ki-67 positive group(67.7% vs 63.2%). Conclusion: In the patients with breast cancer, ER, PR negative ones were more sensitive to neoadjuvant chemotherapy. These patients may get more benefits from chemotherapy. ER, PR could be feasible markers for predicting the effective rate of neoadjuvant chemotherapy.

Expression of BI-1 protein and its significance in breast cancer

Objective： To investigate the correlations of expression of Bax inhibitor-1 （BI-1） gene and the receptors of estrogen and progestogen in breast cancer and its significance. Methods： Immunohistochemical methods had been used to detect the expressions of BI-1 gene and receptors of estrogen and progestogen in breast cancer. Results： The positive rates of expressions of BI-1 gene, estrogen receptor （ER） and progestogen receptor （PR） in breast cancer were 77.08%, 60.42% and 54.17%, respectively. The positive rate of expression of BI-1 gene was higher in the group with negative expression of ER than the positive group, their positive rates were 76.92% and 52.27%, respectively; but there was no statistical difference between the two groups with positive and negative expressions of PR. The positive rate of expression of BI-1 gene was also higher in the group with positive lymph node metastasis than the non-lymph node metastasis group, and their positive rates were 64.58% and 36.36%, respectively. The difference was statistically significant （P 〈 0.05）. Conclusion： BI-1 gene, in combination with ER, has guiding significance for patients with breast cancer to choose individual chemotherapy and radiotherapy after operation and can become an important indicator for judging the prognosis of breast cancer.

Pneumonic benign metastasizing leiomyoma:a case report and clinical treatment

Benign metastasizing leiomyoma （BML） is a rare entity usually occuring in females with history of uterus leiomyoma. It appears as a histopathologic benign smooth muscle tumors, distant from the uterus. It is hormone dependent and progresses slowly. Operation is the main clinical treatment. The article was reported one case who was a thirty-eight years old female. She was found to have bilateral lung nodules after hysterectomy of uterine leiomyoma seven years ago. An open lung biopsy revealed that the nodules consist of proliferating smooth muscle cells with a histopathologic feature which was similar to her uterus leiomyoma. Positive staining of estrogen and progesterone receptors were detected, which proved the turner originate from utedne. The patient did not accept operation, chemotherapy, radiotherapy or other treatment. We still follow up the development of the case.

Effects of Estradiol on 5-HTsA and 5-HT2c Receptor Immunolabeling in Rat Hippocampus

Steroid hormones participate in the modulation of serotonergic transmission, including the regulation of synthetic and metabolic enzyme production, as well as receptor and transporter activity. The changes of 5-HT5A and 5-HT2c immunolabeling induced by steroids in the hippocampus ofovariectomized rats were studied in this work. Densitometric analysis in rat hippocampi were carried out for adjacent brain coronal immunolabeled sections after treatment with subcutaneous injections of vehicle, estradiol, progesterone or the combination of both steroids in ovariectomized rats. Exposure to estradiol and the combination of estradiol and progesterone significantly reduced the 5-HT5A-like immunosignal in the CA 1 region while progesterone did not induce changes. On the other hand, exposure to the combination of estradiol and progesterone or estradiol alone increased the 5-HT2c immunosignal in the same region. These results indicate that estradiol is involved in the discrete regulation of serotonin receptors 5-HT5A and 5-HT2c in rat hippocampus.

Effect of acupuncture on the luteal function of rats with embryo implantation dysfunction

Objective To observe the effects of acupuncture on the luteal function of rats with embryo implantation dysfunction, and to explore its mechanism. Methods The early pregnant rats were randomly divided into normal control group （N）, model group （M）, acupoint group （A）, and non-acupoint group （AC）. The model of embryo implantation dysfunction in Group M, A, and AC was established with Mifepristone. For rats in Group A, bilateral ＂Housanli＂ （后三里 ST 36） and ＂Sanyinjiao＂ （三阴交 SP 6） were needled, while the non-acupoints beside the acupoints were needled in Group AC. In this experiment, the serum levels of luteinizing hormone （LH）, estradiol （E2）, and progesterone （P） were detected with radioimmunoassay, the expression of vascular endothelial growth factor （VEGF） in the rat ovarian tissue was detected by using Western-blot. The mRNA expressions of VEGF and luteinizing hormone receptor （LHR） in the ovarian tissue were detected by using RT-PCR. Results The serum levels of LH and P were significantly higher in group A than in group M and AC （all P〈0.05）, showing no statistical significance when compared with group N. The VEGF content, and expressions of VEGF mRNA and LHR mRNA in the ovarian tissue of group A were significantly elevated than those in group M and group AC （all P〈0.05）, showing no statistical significance when compared with group N. Conclusion Needling at ＂Housanli＂ （后三里 ST 36） and ＂Sanyinjiao＂ （三阴交 SP 6） could elevate the serum levels of LH and P of rats with embryo implantation dysfunction, and up-regulate the expression of LHR mRNA, VEGF and its mRNA in the ovarian tissue. It may enhance the luteal function of rats with embryo implantation dysfunction and improve its embryo implantation environment.

Fractionated evaluation of immunohistochemical hormone receptor expression enhances prognostic prediction in breast cancer patients treated with tamoxifen as adjuvant therapy

Objective： To compare the prognostic prediction between dichotomized and fractionated evaluations of hormone receptor expressions. Methods： Patients with stages Ⅰ-Ⅲ breast cancers, who received adjuvant tamoxifen, were enrolled. The expression of estrogen receptor （ER） and progesterone receptor （PR） was evaluated by immu- nohistochemistry （IHC）. A fractionated score （F score）, the percentage of positive-staining nuclei （0=none, 1=1%-10% 2= 11%-30%, 3=31%-50%, 4=51%-70%, and 5=71%-100%）, was assigned to each case. The dichotomized scoring method defines an F score 〉1 as positive. The prognostic values of both scores were compared by multiple Cox＇s proportional hazard models of disease-free survival （DFS） and overall survival （OS）. Results： Four hundred and six- teen patients with a median follow-up of 78.0 months were included. F scores for ER and PR correlated directly with DFS and OS. Although both the dichotomized and fractionated ER and PR scores were significantly associated with DFS and OS in univariate analyses, only fractionated ER and PR scores remained as independent prognostic factors of DFS and OS in the final multiple Cox＇s proportional hazard models. Conclusion： Fractionated IHC hormone receptor expression evaluation enhances the prognostic prediction compared with a dichotomized assessment.

ANALYSIS OF BREAST CANCER PROFILES USING BAYESIAN NETWORK MODELING

Breast cancer is the leading cause of cancer-related death for women in Tunisia and the prognosis of its metastasis remains a major problem for oncologists despite advances in treatment. In this work we use Bayesian networks to develop a decision support system that is based on the modeling of relationships between key signaling proteins and clinical and pathological characteristics of breast tumors and patients. Motivated by the lack of prior information on the parameters of the problem, we use the Implicit inference for the structure and parameter learning. A dataset of 84 Tunisian breast cancer patients was used and new prognosis factors were identified. The system predicts a metastasis risk for different patients by computing a score that is the joint probability of the Bayesian network using parameters estimated on the learning database. Based on the results of the developed system we identified that overexpression of ErbB2, ErbB3, bcl2 as well as of oestrogen and progesterone receptors associated with a low level of ErbB4 was the predominant profile associated with high risk of metastasis.