The potential mechanism of miR-130b on promotion of the invasion and metastasis of hepatocellular carcinoma by inhibiting Notch-Dll1.

Introduction: This study aimed to elucidate the regulatory role and molecular regulation mechanism of miR-130b gene in the process of invasion and metastasis of hepatocarcinoma, and provide a theoretical basis for seeking of effective prevention and treatment of new targets for hepatocellular carcinoma.Materials and methods: The expression level of miR-130b gene in hepatocarcinoma tissues was determined by qRT-PCR. The biological function and mechanism of miR-130b gene were verified by cell and animal models, and the target gene was verified by double luciferase assay.Results: In the liver cancer tissues of patients with metastasis, the expression level of miR-130b gene was increased, and the difference was significantly significant (p < 0.05). Evaluation of independent risk factors for overall survival showed significant difference (p < 0.01). Up-regulation of miR-130b in MHCC97L- subpopulation cells significantly enhanced the invasion and migration ability, and the difference was statistically significant (p < 0.05). The invasion and migration ability of MHCC97H + subpopulation cells with increased expression of miR-130b was significantly decreased, and the difference was notably significant (p < 0.05). When the expression of miR-130b in MHCC97H + subpopulation cells was inhibited, the expressions of Notch-Dll1 and SOX2, Nanog and E2F3 proteins in transplanted tumor tissues were significantly higher than those in other groups (p < 0.05). When miR-130b in MHCC97L- subpopulation cells was up-regulated, the expressions of Notch-Dll1 and Bcl-2, CCND1, Nanog and MET proteins in transplanted tumor tissues were significantly increased than those in other groups (p < 0.05). The prediction results of bioinformatics data suggest that the target gene of miR-130b may be Notch-Dll1 gene. The experiment of luciferase reporter gene confirmed that miR-130b gene can be inhibited and contains fluorescent reporter gene with complementary binding site, lost activity.Conclusion: The miR-130b gene can inhibit the protein expression of Notch-Dll1, and it can promote the invasion and metastasis of liver cancer cells.

Hepatectomy for liver metastases from gastric cancer: a systematic review.

BACKGROUND: Official guidelines recommend palliative treatments for patients with liver metastases from gastric cancer. However, many case series reported that hepatectomy for such cases is safe and effective. This systematic review compares the overall survival between hepatectomy and palliative therapy in patients with liver metastases from gastric cancer. METHODS: Two independent reviewers performed a systematic search of literature in EMBASE and PubMed, updated until 26 October 2016. The Newcastle-Ottawa score for cohort studies was used for quality assessment of included studies. RESULTS: A total of eight cohort studies involving 196 patients in the hepatectomy arm and 481 in the palliative arm were included. Median overall survival of patients in the two arms was 23.7 (range, 13.0 to 48.0) and 7.6 (range, 5.5 to 15.2), respectively. Median rates of overall survival of the two arms were 69, 40, 33 and 27, 8, 4% at 1, 2, and 3 years, respectively. Comparing with palliative therapy, hepatectomy was associated with significantly lower mortality at 1 year (odds ratio 0.17, P < 0.001) and 2 years (odds ratio 0.15, P < 0.001). Among the patients who underwent hepatectomy, Asian cohorts showed higher median rates of overall survival than Western cohorts at 1 year (76 vs. 60%), 2 years (47 vs. 30%) and 3 years (39 vs. 23%). CONCLUSIONS: Hepatectomy in the management of liver metastases from gastric cancer can be considered effective. In the elective setting, hepatectomy provides a potential alternative to palliative therapy.

Clinicopathological characteristics and liver stem cell marker expression in hepatocellular carcinoma involving bile duct tumor thrombi.

The aim of this study was to analyze the clinicopathological characteristics and expression of liver stem cell markers of hepatocellular carcinoma (HCC) involving bile duct tumor thrombi (BDTT). A total of 35 patients with HCC and BDTT in a consecutive series of HCC patients who underwent surgical treatment were studied retrospectively and compared with 916 patients without BDTT from the same series. Clinicopathological characteristics, overall survival (OS), and tumor expression of liver stem cell markers CD133, CD90, EpCAM, CK19, VEGF, and C-kit were compared between the two patient groups. Analysis was performed for the entire patient groups as well as for 35 pairs of patients with or without BDTT matched by propensity score. HCC patients with BDTT tended to have smaller tumors than those without BDTT, as well as a higher probability of having poorly differentiated tumor, Child-Pugh class B, liver cirrhosis, and microvascular invasion. Tumor tissue in patients with BDTT showed significantly higher expression rates of all liver stem cell markers examined. OS was significantly lower for patients with BDTT at 1 year (69 vs 84 %), 3 years (37 vs 64 %), and 5 years (20 vs 55 %) (P < 0.001). Patients with HCC and BDTT show lower OS than patients without BDTT. The higher frequency of liver stem cell marker expression in the presence of BDTT suggests that such stem cells may play a role in the pathogenesis of this form of HCC.

Combination of 5-fluorouracil and 2-morphilino-8-phenyl-4H-chromen-4-one may inhibit liver cancer stem cell activity.

This work aims to evaluate the impact of 2-morpholino-8-phenyl-4H-chromen-4-one (LY294002) combined 5-fluorouracil (5-FU) for the activity of CD90+ liver cancer cells derived from the human liver cancer cell line MHCC97H. MHCC97H sphere-forming cells (MSFCs) were amplified in serum-free medium and CD90+ cells were isolated from bulk MSFCs using flow cytometry. The phenotype of these CD90+ cells which show liver cancer stem cells (LCSCs) behavior was validated in vitro and in a xenograft model in nude mice. MSFCs, CD90+ liver cancer cells (CD90+ LCCs), and parental MHCC97H cells were treated with no drug, LY294002 alone, 5-FU alone, or both drugs together and then compared in terms of stem cell-related gene expression, proliferation, and invasion. Stem cell phenotype increased with increasing proportion of CD90+ cells, in ascending order: parental MHCC97H cells, MSFCs, and CD90+ liver cancer cells. LY294002 reduced the expression of CD90, Nanog, SALL4, and SHP2 in a concentration-dependent manner in CD90+ LCCs and MSFCs, but not in parental cells. LY294002 blocked AKT phosphorylation via the PI3K/AKT signaling pathway and inhibited CD90+ LCCs proliferation and tumorigenicity in vitro and in vivo. CD90+ liver cancer cells can express liver cancer stem cell phenotype. LY294002 inhibits the proliferation and invasion of MHCC97H-derived CD90+ LCCs and sensitized CD90+ LCCs-derived tumors to 5-FU in the current study which may provide insight into the association between the LY294002 combined 5-FU and liver cancer stem cell (LCSCs).

Association between age and overall survival of patients with hepatocellular carcinoma after hepatic resection.

AIM: The suitability of hepatic resection for older patients remains controversial. This study aimed to investigate whether age influences overall survival of patients with hepatocellular carcinoma (HCC) after resection. METHODS: Records of 1,132 patients with HCC after hepatic resection were retrospectively reviewed. Overall survival (OS) was compared between younger and older patients based on five cut-off ages (30, 40, 50, 60, and 70 years). RESULTS: Across all patients, OS was 89.7% at 1 year, 67.7% at 3 years, and 47.7% at 5 years. OS was similar between younger and older patients at all cut-off ages (all P > 0.1), but OS was marginally lower among patients >70 years old than those ≤70 (P = 0.090). Multivariate analyses identified several risk factors for lower OS: preoperative serum albumin <35 g/L, alanine aminotransferase >80 U/L, α-fetoprotein ≥400 ng/ml, presence of esophagogastric varices or macrovascular invasion, incomplete/absent tumor capsule, tumor size >10 cm, tumor number ≥3, and major hepatectomy. CONCLUSION: Age does not influence the prognosis of patients with HCC after hepatic resection. Older patients should be considered for curative resection if remnant liver volume and liver function are adequate. J. Surg. Oncol. 2016;114:966-970. © 2016 Wiley Periodicals, Inc.

Prognostic factors of regression and relapse of complex atypical hyperplasia and well-differentiated endometrioid carcinoma with conservative treatment.

OBJECTIVE: To evaluate possible prognostic factors regarding regression and relapse of complex atypical hyperplasia (CAH) and well-differentiated endometrioid adenocarcinoma (WDC) treated with conservative treatment. METHODS: The retrospective study reviewed clinicopathologic, treatment, regression and relapse data from patients diagnosed with CAH or WDC who were treated with conservative treatment at 4 institutions. Potential factor evaluation was performed. SPSS 16 was used for statistical analyses. RESULTS: Eighty-eight patients were included (51 had WDC, and 37 had CAH). Regression was evaluated in 88 patients, with a median follow-up of 61 (range 15-95) months. Seventy-seven (87.5%) patients regressed, and 11 (12.5%) had persistent or progressive disease. Univariate and multivariate analyses showed no factors associated with regression. Relapse was evaluated in 71 patients, with median follow-up of 54 (range 8-86) months. Twenty-five/71 (35.2%) patients experienced relapse. On univariate analysis, body mass index (BMI) 30 or higher (p=0.001), WCD at initial biopsy (p=0.017) and positive expression of post-treatment ki67 (p=0.033) were associated to a higher relapse probability. However, only BMI 30 or higher was significant on multivariate analysis (p=0.012). The Kaplan-Meier analysis revealed a higher relapse probability in the patients with BMI 30 or higher (p=0.001). CONCLUSION: Obesity seems to be a risk factor for relapse of CAH or WDC with conservative treatment.

A meta-analysis of the relationship between glutathione S-transferases gene polymorphism and hepatocellular carcinoma in Asian population.

The results from the published studies on the association between glutathione S-transferases (GST) gene polymorphism and hepatocellular carcinoma (HCC) in Asian population are still conflicting. GSTM1, GSTT1 and GSTP1 are the mainly mutant sites reported at present. This meta-analysis was performed to evaluate the relationship between GST gene polymorphism and HCC risk in Asians. Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) on February 1, 2012, and eligible investigations were synthesized using meta-analysis method. Results were expressed with odds ratios (OR) for dichotomous data, and 95 % confidence intervals (CI) were also calculated. Twenty-five investigations were identified for the analysis of association between polymorphic deletion of GSTM1 and HCC, consisting of 3,547 patients with HCC and 6,132 controls. There was a marked association between GSTM1 null genotype and HCC susceptibility (OR 1.48, 95 % CI 1.19-1.85, P = 0.0004). GSTM1 null genotype was associated with HCC risk in Chinese. Furthermore, null genotype of GSTT1 was associated with HCC susceptibility in Asians. For the GSTM1-GSTT1 interaction analysis, the dual null genotype of GSTM1/GSTT1 was significantly associated with HCC susceptibility in Asian population. However, GSTP1 ile105 val gene polymorphism was not associated with HCC risk in Asian population. In conclusion, GSTM1/GSTT1 null genotype is associated with the HCC susceptibility. However, GSTP1 gene polymorphism is not associated with HCC risk.

Evaluation of risk factors and clinicopathologic features for intrahepatic cholangiocarcinoma in Southern China: a possible role of hepatitis B virus.

BACKGROUND: Recent efforts suggest an etiologic role of hepatitis B virus (HBV) infection in intrahepatic cholangiocarcinoma (ICC) and the involvement of hepatic progenitor cell in ICC development, without definitive conclusions. This case-control study was undertaken to investigate risk factors for ICC, and clinicopathological features of HBV-associated ICC were analyzed. METHODS: The report comprised 98 patients with pathologically confirmed ICC and 196 healthy control subjects. Logistic regression was used to determine odds ratios and 95% confidence intervals. The sex and age distributions of HBV-related and unrelated ICC patients were compared respectively with those of 882 HBV-associated hepatocellular carcinoma patients from a random selection, and the clinicopathological data of 62 ICC patients with or without HBV infection undergoing surgical resection were compared. RESULTS: There was an association between ICC and each of HBV infection, liver cirrhosis, hepatolithiasis, and liver fluke infestation with the odds ratios (95% confidence intervals) of 2.75 (1.27-5.95), 8.42 (2.50-28.37), 22.81 (7.16-72.68), and 3.55 (1.60-7.89), respectively, with a marked synergism of cirrhosis and HBV infection (20.67; 5.40-79.06). Compared with HBV-unrelated ICC patients, HBV-related ICC patients were more common in male and younger subjects, had a higher incidence of abnormal serum alfa-fetoprotein level, cirrhosis, and neutrophilic infiltration, and had a lower proportion of elevated carbohydrate antigen 19-9 (CA19-9) values. CONCLUSIONS: The independent association of HBV infection with ICC, synergy between cirrhosis and HBV infection, and some clinicopathological similarities between HBV-related ICC and hepatocellular carcinoma suggests that both may share similar or common tumorigenic process and may possibly originate from malignant transformation of hepatic progenitor cell.

[Synthesis of colon-specific prodrug of indomethacin and its inhibitory effect on liver metastasis from colon cancer].

OBJECTIVE: To develop a colon-specific prodrug of Indomethacin microbially triggered, carry out in vitro/in vivo evaluation of drug release, and appraise its inhibitory effect on liver metastasis from colon cancer. METHODS: Indomethacin prodrugs were synthesized and characterized by FTIR and NMR, and dissolution test simulating gastrointestinal tract was employed to screen the colon-specific prodrug. Then, the pharmacokinetic profile of portal vein and peripheral blood in Sprague-Dawley rats was studied. Lastly, the inhibitory effect on liver metastasis from colon cancer in nude mice was observed. RESULTS: The chemical structure characterized by FTIR and NMR demonstrated that six kinds of indomethacin-block-amylose with different drug loading (IDM-AM-1-6) were synthesized, among which IDM-AM-3 was degraded 1.3%, 9.3% and 95.3%, respectively, in simulated gastric fluid for 4 h, small intestine for 6 h, and colon for 36 h. The pharmacokinetic test of IDM-AM-3 showed that absorption was delayed significantly (P < 0.01), peak time [(11.35 + or - 2.45) h], elimination half-life [(16.74 + or - 4.04) h] and mean residence time [(22.27 + or - 0.52) h] were significantly prolonged (P < 0.01), as well as peak serum concentrations [(9.69 + or - 2.40) mg/L] and AUC(0-t) [(236.7 + or - 13.1) mg x L(-1) x h] were decreased markedly (P < 0.01) as compared with those of IDM regarding to portal vein. Additionally, its AUC(0-t) in peripheral blood was remarkably lower than that in Portal vein (P < 0.01). The tumor suppression observation showed that it could remarkably reduce the number of liver metastases in contrast to IDM (P < 0.05). CONCLUSION: Colon-specific IDM-AM-3 possesses advantage of sustained release in portal vein providing some experimental basis for colon-specific delivery system applied to sustained release in the portal vein.

Serum Prealbumin is Negatively Associated with Survival in Hepatocellular Carcinoma Patients after Hepatic Resection.

Objective: Low serum prealbumin levels are associated with poor prognoses in some type of cancers. However, the role of prealbumin in patients with hepatocellular carcinoma (HCC) is unknown. The present study aimed to investigate the role of serum prealbumin levels in long-term survival for HCC patients after hepatic resection. Methods: HCC patients who underwent hepatic resection from June 2007 to December 2015 were retrospectively analyzed in a tertiary liver center. Patients were classified as having normal or reduced serum prealbumin based on a cut-off value of 200 mg/L. Overall survival and recurrence rate were analyzed between groups. Propensity score analysis was used to reduce bias due to other patient differences at baseline. Results: A total of 1349 HCC patients who underwent hepatic resection were enrolled on this study, including 1168 (86.6%) male and 181 (13.4%) female. Patients with normal serum prealbumin had significantly higher overall survival than those with reduced serum prealbumin (P < 0.001). Similar findings were observed after propensity analysis and subgroup analysis based on liver cirrhosis. Moreover, patients with normal serum prealbumin had a significantly lower recurrence rate than those with reduced serum prealbumin (P < 0.001). Conclusions: Low preoperative level of serum prealbumin is associated with poor long-term survival in patients with HCC after hepatic resection. Low serum prealbumin may be a marker to identify patients at high risk of poor prognosis after hepatic resection.

Preoperative evaluation with T-staging system for hilar cholangiocarcinoma.

AIM: To investigate the clinical value of T-staging system in the preoperative assessment of hilar cholangiocarcinoma. METHODS: From March 1993 to January 2006, 85 patients who had cholangiocarcinoma diagnosed by operative tissue-biopsy were placed into one of three stages based on the new T-staging system, and it was evaluated the resectability and survival correlated with T-staging. RESULTS: The likelihood of resection and achieving tumor-free margin decreased progressively with increasing T stage (P < 0.05). The cumulative 1-year survival rates of T1, T2 and T3 patients were 71.8%, 50.8% and 12.9% respectively, and the cumulative 3-year survival rate was 34.4%, 18.2% and 0% respectively; the survival of different stage patients differed markedly (P < 0.001). Median survival in the hepatic resection group was greater than in the group that did not undergo hepatic resection (28 mo vs 18 mo; P < 0.05). The overall accuracy for combined MRCP and color Doppler Ultrasonagraphy detecting disease was higher than that of combined using CT and color Doppler Ultrasonagraphy (91.4% vs 68%; P < 0.05 ). And it was also higher in detecting port vein involvement (90% vs 54.5%; P < 0.05). CONCLUSION: The proposed staging system for hilar cholangiocarcinoma can accurately predict resectability, the likelihood of metastatic disease, and survival. A concomitant partial hepatectomy would help to attain curative resection and the possibility of long-term survival. MRCP/MRA coupled with color Doppler Ultrasonagraphy was necessary for preoperative evaluation of hilar cholangiocarcinoma.

Is laparoscopic hepatectomy superior to open hepatectomy for hepatocellular carcinoma?

The low perioperative morbidity and shorter hospital stay associated with laparoscopic hepatectomy have made it an often-used option at many liver centers, despite the fact that many patients with hepatocellular carcinoma have cirrhosis, which makes the procedure more difficult and dangerous. Type of surgical procedure proves not to be a primary risk factor for poor outcomes after hepatic resection for hepatocellular carcinoma, the available evidence clearly shows that laparoscopic hepatectomy is an effective alternative to the open procedure for patients with early-stage hepatocellular carcinoma, even in the presence of cirrhosis. Whether the same is true for patients with intermediate or advanced disease is less clear, since laparoscopic major hepatectomy remains a technically demanding procedure.

Harms and benefits of adoptive immunotherapy for postoperative hepatocellular carcinoma: an updated review.

The harms and benefits of adoptive immunotherapy (AIT) for patients with postoperative hepatocellular carcinoma (HCC) are controversial among studies. This study aims to update the current evidence on efficacy and safety of AIT for patients with HCC who have received curative therapy. Electronic databases were systematically searched to identify randomized controlled trials (RCTs) and cohort studies evaluating adjuvant AIT for patients with HCC after curative therapies. Recurrence and mortality were compared between patients with or without adjuvant AIT. Eight RCTs and two cohort studies involving 2,120 patients met the eligibility criteria and were meta-analyzed. Adjuvant AIT was associated with significantly lower recurrence rate than curative therapies alone at 1 year [risk ratio (RR) 0.64, 95%CI 0.49-0.82], 3 years (RR 0.85, 95%CI 0.79-0.91) and 5 years (RR 0.90, 95%CI 0.85-0.95). Similarly, adjuvant AIT was associated with significantly lower mortality at 1 year (RR 0.64, 95%CI 0.52-0.79), 3 years (RR 0.73, 95%CI 0.65-0.81) and 5 years (RR 0.86, 95%CI 0.79-0.94). Short-term outcomes were confirmed in sensitivity analyses based on RCTs or choice of a fixed- or random-effect meta-analysis model. None of the included patients experienced grade 3 or 4 adverse events. Therefore, this update reinforces the evidence that adjuvant AIT after curative treatment for HCC lowers risk of recurrence and mortality.

Tumor stage and primary treatment of hepatocellular carcinoma at a large tertiary hospital in China: A real-world study.

The current clinical reality of tumor stages and primary treatments of hepatocellular carcinoma (HCC) is poorly understood. This study reviewed the distribution of tumor stages and primary treatment modalities among a large population of patients with primary HCC. Medical records of patients treated between January 2003 and October 2013 for primary HCC at our tertiary hospital in China were retrospectively reviewed. A total of 6241 patients were analyzed. The distribution of Barcelona Clinic Liver Cancer (BCLC) stages was as follows: stage 0/A, 28.9%; stage B, 16.2%; stage C, 53.6%; stage D, 1.3%. The distribution of Hong Kong Liver Cancer (HKLC) stages was as follows: stage I, 8.4%; stage IIa, 1.5%; stage IIb, 29.0%; stage IIIa, 10.0%; stage IIIb, 33.6%; stage IVa, 3.4%; stage IVb, 2.5%; stage Va, 0.2%; stage Vb, 11.4%. The most frequent therapy was hepatic resection for patients with BCLC-0/A/B disease, and transarterial chemoembolization for patients with BCLC-C disease. Both these treatments were the most frequent for patients with HKLC I to IIIb disease, while systemic chemotherapy was the most frequent first-line therapy for patients with HKLC IVa or IVb disease. The most frequent treatment for patients with HKLC Va/Vb disease was traditional Chinese medicine. In conclusion, Prevalences of BCLC-B and -C disease, and of HKLC I to IIIb disease, were relatively high in our patient population. Hepatic resection and transarterial chemoembolization were frequent first-line therapies.

Optimizing stage of single large hepatocellular carcinoma: A study with subgroup analysis by tumor diameter.

This study aims to refine the designation for single hepatocellular carcinoma (HCC) >5 cm by comparing the postresection prognosis of these patients with those who have a single-tumor ≤5 cm and those with stage B.Patients with a single-tumor were classified into subgroups based on diameter. Of the 1132 patients analyzed, 426 had a single-tumor >2 and ≤5 cm; 229, a single-tumor >5 and ≤8 cm; 52, a single-tumor >8 and < 10 cm; 150, a single-tumor ≥10 cm; and 275, stage B.Hospital mortality and complications increased with tumor size among the single-tumor subgroups and median survival decreased with increasing of tumor size. Overall survival (OS) among patients with a single-tumor >5 cm was significantly lower than among patients with a single-tumor >2 and ≤5 cm (P ≤ .001), but significantly higher than among patients with clearly stage B (P ≤ .001). Patients with a single-tumor >5 and ≤8 cm showed lower OS than patients with a single-tumor >2 and ≤5 cm (P < .001). Patients with a single-tumor >8 and <10 cm or a single-tumor ≥10 cm showed lower OS than patients with a single-tumor >5 and ≤8 cm (P = .033 and .006), and similar OS to patients with stage B (P = .323).Patients with a single-tumor >5 and ≤8 cm may be assigned to a new stage between early and intermediate. Patients with a single-tumor >8 cm may be assigned to intermediate stage.

Preoperative Ratio of Neutrophils to Lymphocytes Predicts Postresection Survival in Selected Patients With Early or Intermediate Stage Hepatocellular Carcinoma.

This study aims to clarify the prognostic value of the preoperative neutrophil-to-lymphocyte ratio (NLR) for patients with hepatocellular carcinoma (HCC) after potentially curative hepatic resection (HR). The prognostic value of the NLR for HCC patients has not been definitely reviewed by large studies, especially for those with different Barcelona Clinic Liver Cancer (BCLC) stages.A consecutive sample of 963 HCC patients who underwent potentially curative HR was classified as having low or high NLR using a cut-off value of 2.81. Overall survival (OS) and tumor recurrence were compared for patients with low or high NLR across the total population, as well as in subgroups of patients in BCLC stages 0/A, B, or C. Clinicopathological parameters, including NLR, were evaluated to identify risk factors of OS and tumor recurrence after potentially curative hepatic resection. Multivariate analyses were performed using the Cox proportional hazards model or subdistribution hazard regression model.Multivariate analyses showed that NLR (>2.81), tumor number (>3), incomplete capsule, serum albumin (≤35 g/L), alanine transaminase activity (>40 U/L), and macrovascular invasion were risk factors for low OS, whereas NLR (>2.81), tumor size (>5 cm), alpha fetal protein concentration (>400 ng/L), and macrovascular invasion were risk factors for low tumor recurrence. NLR > 2.81 was significantly associated with poor OS and tumor recurrence in the total patient population (both P < 0.001), as well as in the subgroups of patients in BCLC stages 0/A or B (all P < 0.05). Moreover, those with high NLR were associated with low OS (P = 0.027), and also with slightly higher tumor recurrence than those with low NLR for the subgroups in BCLC stage B (P = 0.058). Neither association, however, was observed among patients with BCLC stage C disease.NLR may be an independent predictor of low OS and tumor recurrence after potentially curative HR in HCC patients in BCLC stages 0/A or B.

Discordances in ER, PR and HER2 receptors between primary and recurrent/metastatic lesions and their impact on survival in breast cancer patients.

The aim of this study was to evaluate the frequency and prognostic impact of changes in the estrogen (ER), progesterone (PR) and human epidermal growth factor receptor 2 (HER2) status between primary and recurrent/metastatic lesions (RML). We investigated 133 breast cancer patients for ER, PR and HER2 status of primary and RML and their follow-up records. Among 133 patients with RML, discordance rate for ER, PR, and HER2 was 18.8, 33.8, and 6.8%, respectively. ER, PR and HER2 discordance were observed in 20.0, 38.1 and 6.7% of the patients with distant metastasis, and in 14.3, 17.9 and 7.1% of the patients with locoregional recurrence. The mean time between the primary diagnosis and last contact or death was 57 (range 22-78) months and between the recurrence biopsy and last contact or death was 17 (range 1-33) months. Among 133 patients with RML, the ER-discordant cases and ER-loss cases experienced a worse overall survival (OS) (p=0.001 and p=0.016, respectively) and post-recurrence survival (PRS) (p=0.001 and p=0.018, respectively), compared with the respective concordant cases. The HER2-discordant patients and HER2-loss patients had a poorer OS (p=0.008 and p=0.001, respectively) and PRS (p=0.004 and p=0.000, respectively) than the respective concordant cases. Among 105 patients with distant metastasis, ER discordance, ER loss, HER2 discordance and HER2 loss, compared with the respective concordant cases, resulted in a worse OS and PRS (p<0.05 for all). Our findings show an evident change in ER, PR and HER2 between breast primary tumors and relapsing tumors. The unstable status for ER or HER2 in breast cancer seems to be clinically significant and to correlate with a worse prognosis.