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The transforming growth factor β1 (TGF-β1) and CD8-positive T cells are two important immune factors that function at opposite directions. The purpose of this study was to verify the relationship between the two factors and their associations with long-term effects of adjuvant chemotherapy or endocrine therapy in breast cancer. Expression of TGF-β1 precursor and CD8 was immunohistochemically detected on surgically-obtained tumor samples of 130 (stage I-III) invasive breast carcinomas from Chinese subjects, who were followed up for a mean time of 112 months. Interstitial CD8-positive cells and TGF-β1 precursor-positive cells adjacent to tumor nests were counted. Infiltration of CD8-positive lymphocytes into tumor nests and TGF-β1 precursor expression in tumor cells were observed and survival analysis was performed. Our results showed that density of interstitial CD8-positive lymphocytes was an independent adverse prognostic factor for distant disease-free survival (DDFS) (HR=8.416, 95% CI=1.636-43.292, P=0.011) in hormone receptor-positive patients who were on adjuvant endocrine therapy. For breast cancer patients who did not receive adjuvant chemotherapy, those without infiltration of CD8-positive cells into tumor nests had a shorter overall survival (OS) than their counterparts with CD8-positive cell infiltration into tumor nests (Log-Rank, P=0.003). But OS of patients without infiltration of CD8-positive cells into tumor nests was significantly prolonged by adjuvant chemotherapy (Log-Rank, P=0.013) and paralleled that of patients with CD8-positive cell infiltration. Although OS was shorter in the tumor cell TGF-β1 precursor (t-TGF-β1-pre)-positive patients than in the negative patients in patients without receiving chemotherapy (P=0.053), OS of t-TGF-β1-pre-positive patients was significantly prolonged by adjuvant chemotherapy (P=0.035) and was longer than that of t-TGF-β1-pre-negative patients. Analysis showed that t-TGF-β1-pre was an independent positive prognostic factor for DDFS (HR=0.392 95% CI=0.157-0.978, P=0.045) in patients who received adjuvant chemotherapy. This study suggested that density of interstitial CD8-positive lymphocytes was of prognostic value in hormone receptor-positive patients who received adjuvant endocrine therapy. Our study verified that adverse immunologic signatures consisting of absence of CD8-positive cells in tumor nests or expression of TGF-β1 precursor in tumor cells in breast cancer were associated with worse prognosis and significantly improved long-term survival with adjuvant chemotherapy, respectively.

Papillary renal cell carcinoma (PRCC) is traditionally classified into type 1 and type 2. Recently, an oncocytic variant of PRCC has been described. We report a series of 6 oncocytic renal papillary tumors (OPRCC) which tended to occur in older patients (mean, 56.8 years) with a male preference (male-to-female ratio is 5:1). All 6 patients are alive with no evidence of disease after initial resection, showing an indolent clinical behavior. Histologically, tumors exhibited predominant papillary structure with delicate fibrovascular cores. Papillae were lined by single layers of cells with large, deeply eosinophilic and finely granular cytoplasms and round regular nucleus. The phagocytosis of tumor cells was frequently and evidently seen in our cases that hemosiderin-laden tumor cells and foamy tumor cells were noticed in five and four cases respectively. All tumors were immunoreactive for racemase, vimentin, CD10, and MET and negative for CD117. While E-cadherin, EMA, and cytokeratin 7 exhibited variable immunopositivity. FISH analysis was performed in five of six cases and found heterogeneous results. Trisomy of chromosomes 7 was found in three cases and trisomy of chromosomes 17 in two cases. Loss of chromosome Y was noted in one of four tumors in male patients. MET gene status was also investigated by direct sequencing in all 6 cases and found no distinct mutation in any case. These results suggest that OPRCC shows distinct morphology, indolent clinical behavior, and similar immunohistochemical and cytogenetic features with PRCC, seems to be a variant in the PRCC group. Whether the strong expression of MET indicates a potential therapeutic target is still unknown and requires further investigation in clinical trials.

Objectives: To determine the distribution of macrophages (MΦ) in both xanthogranulomatous cholecystitis (XGC) and gallbladder carcinoma (GBC) and to analyze the association between XGC and GBC., Methods: From January 2009 to June 2011, 110 patients with gallbladder diseases, including 35 with GBC, 45 with XGC and 30 with chronic cholecystitis (CC), were enrolled. Immunohistochemistry stain and real-time polymerase chain reaction using oncogenes (BCL-2, c-Myc) and anti-oncogene genes (p53, p21) were performed, serum expressions of tumor marker (CA19-9, CA724 and CA242) were also conducted. MΦ were used to determine their potential role in the carcinogenesis of GBC., Results: BCL-2 and c-Myc expressions gradually increased among CC, XGC and GBC (P = 0.032 and P = 0.020, respectively); while p53 and p21 were similar in the three groups (P = 0.167 and P = 0.122, respectively). Serum BCL-2 and c-Myc were significantly correlated with their tissue levels; in terms of serum tumor markers, which gradually increased among CC, XGC and GBC, however, CA242 and CA724 were both negative in XGC but positive in GBC. Furthermore, gradually increasing MΦ counts were observed among CC, XGC and GBC groups; c-Myc and CA724 were independent predictors for the differentiation of XGC and GBC., Conclusions: XGC is an uncommon inflammatory condition distinct from CC and may be associated with the precancerous nature of GBC for its upregulated oncogenes and MΦ biology. c-Myc and CA724 were independent predictors for the differentiation of XGC and GBC., (© 2012 The Authors. Journal of Digestive Diseases © 2012 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

The purpose of this study was to evaluate the importance of biological markers to predict pathologic complete response (pCR) to neoadjuvant docetaxel plus epirubicin combination chemotherapy in patients with locally advanced breast cancer (LABC). Two hundred and twenty consecutive patients with LABC who had received neoadjuvant chemotherapy (NCT) with docetaxel and epirubicin from March 2006 to March 2009 were included in this retrospective study. The pre- and post-neoadjuvant chemotherapy (NCT) treatment expression levels and changes of Ki-67 proliferation index, estrogen receptor (ER), progesterone receptor (PgR), epidermal growth factor receptor 2 (HER-2), cyclin D1, and nm23-H1 were detected by immunohistochemistry (IHC). The pCR rate was 9.1% (95% CI, 5.3-12.9%). In univariate analysis, poor tumor differentiation, OR after 2 cycles of NCT, both negative of ER/PgR, negative HER-2, positive cyclin D1, and positive nm23-H1 were found to be significantly predictive of a pCR. Histological grade and ER/PgR status were significant for pCR on multivariate analysis (P = 0.023 and 0.003, respectively). The expression levels of cyclin D1 (median, 8% vs. 9%; P = 0.016) after NCT treatment increased significantly, while the median Ki-67 proliferation index was dramatically decreased after NCT treatment from 35 to 15% (P = 0.036). However, after a Bonferroni adjustment, only the difference of Ki-67 proliferation index was still significant (P = 0.026). Histological grade and ER/PgR status are independent predictive factors of pCR to neoadjuvant docetaxel plus epirubicin combination chemotherapy in locally advanced breast cancer. Expression of HER-2, Ki-67, cyclin D1, and nm23-H1 were not predictive for pCR.

The purpose of this study was to evaluate the importance of biological markers to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) in patients with locally advanced breast cancer (LABC) One hundred and twelve consecutive patients with clinical stage III LABC who had received NCT with docetaxel and epirubicin from March 2006 to March 2009 were included in this retrospective study. The pre-NCT treatment expression levels of Ki-67 proliferation index, estrogen receptor (ER), progesterone receptor (PgR), epidermal growth factor receptor 2 (HER-2), Topoisomerase II alpha (Topo-II), and nm23-H1 were detected by immunohistochemistry (IHC). A total of 361 cycles were administered with the median number of three cycles per patient (range, 2-6). The pCR rate was 9.8% (95% CI, 4.3-15.3%). In univariate analysis, poor tumor differentiation, both negative of ER/PgR, negative Topo-II, and positive nm23-H1 were found to be significantly predictive of a pCR. ER/PgR status and nm23-H1 were significant for pCR on multivariate analysis (P = 0.006 and 0.025, respectively). ER/PgR status and nm23-H1 are independent predictive factors of pCR to neoadjuvant docetaxel plus epirubicin combination chemotherapy in patients with LABC.