Clinicopathologic Features and Immune Cell Subtypes Analysis of Tumor-infiltrating Lymphocytes Rich Invasive Breast Carcinoma of No Special Type.

Tumor-infiltrating lymphocytes (TILs) rich invasive breast carcinoma no special type (IBC-NST) is an updated name introduced in the fifth edition WHO classification of breast tumors. Typical medullary breast carcinoma (MBC) represents one end of the spectrum of TILs-rich IBC-NST rather than a distinct morphologic subtype in the new category. A total of 42 cases of MBC and 180 cases of high-grade triple-negative breast cancer (TNBC) without medullary features were included. All samples were stained for CD20, CD4, CD8, and FoxP3 by immunohistochemistry staining. TILs infiltration was more prominent in the MBC tumor nests and in the stroma of high-grade TNBC without medullary features. The average stromal TILs percentage was 78.10% and 61.33%. MBC showed significantly lower numbers of lymphocytes expressing FoxP3 ( P < 0.001), no significant difference in the number of CD4 ( P = 0.154), CD8 ( P = 0.199), and a significantly higher CD8/FoxP3 ratio ( P < 0.001) than the other high-grade TNBC. MBC cases demonstrated less aggressive features such as lower TNM stage ( P = 0.031), smaller tumor size ( P = 0.010), and negative lymph node status ( P = 0.021) than the other high-grade TNBC. The 5-year disease-free survival and overall survival were significantly higher for MBC 82.50% and 85.00% compared with the other high-grade TNBC(54.49% and 58.68%). MBC is mostly triple-negative with higher nuclear atypia. Despite advanced staging based on cell morphology, it has low malignancy and a good prognosis. Differences in biological features and prognosis between MBC and high-grade TNBC without medullary features may be associated with the composition and function of TILs. Immune cell subtypes are complex in TILs-rich IBC-NST and deserve further investigation.

The synthesis of anticancer sulfonated indolo[2,1-a]isoquinoline and benzimidazo[2,1-a]isoquinolin-6(5H)-ones derivatives via a free radical cascade pathway.

A facile CuBr2 induced radical relay addition/cyclization of activated alkenes with substituted-thiosulfonates has been achieved, leading to a broad range of sulfonated indolo[2,1-a]isoquinolines and benzimidazo[2,1-a]isoquinolin-6(5H)-ones in moderate to good yields. In particular, some compounds exhibit bioactivity against cancer cell lines. This protocol shows advantages of low-cost, base-free, simple operation, and broad functional group tolerance.

[Expression of AXIN and MACC1 in Gastric Carcinoma and Its Clinical Significance].

OBJECTIVE: To investigate the expression of axis inhibition protein (AXIN) and metastasis-associated in colon cancer-1 (MACC1) in gastric carcinoma and their relationship to the clinicopathologic characteristics. METHODS: Expressions of AXIN and MACC1 proteins were examined by immunohistochemistry containing 100 specimens of gastric tissues (gastric carcinoma group) and 60 specimens of normal gastric mucosa tissues (control group,the nearby tissues of the excised specimen of gastric cancer patients,from the tumor of the gastric cancer >5.0 cm,and confirm that there were no cancer cells). RESULTS: The positive rates of AXIN and MACC1 proteins in gastric carcinoma and the control tissues were 37.0% vs. 83.3% and 58.0% vs. 6.7%,respectively. The difference were significant between the two groups (both P<0.05). The expressions of AXIN and MACC1 proteins were significantly related with grades of tumor,depth of invasion,lymph node metastasis,and Duke stages ( P<0.05). Spearman analysis showed that there was a negative relationship between the AXIN expression and MACC1 expression (r=-0.355, P<0.05). Kaplan-Meier survival analysis and log-rank single factor analysis showed that AXIN and MACC1 protein expressions were related to the 5-year survival rate of patients (both P<0.05). Cox regression analysis showed that the positive expression of AXIN and the negative expression MACC1 protein,and Duke stages (Ⅲ-Ⅳ) were the independent prognostic factors of gastric carcinoma. CONCLUSION: The expressions of AXIN and MACC1 proteins are related to the prognosis of gastric carcinoma patients,and are involved in the invasion and metastasis of gastric carcinoma.

[Expressions of MACC1, Snail, and KISS-1 Proteins in Infiltrating Breast Carcinoma and Its Clinicopathological Features].

OBJECTIVES: To investigate the protein expressions of metastasis-associated in colon cancer 1 (MACC1), KISS-1 (a cancer ruppressor gene) and Snail (the marker of epithelial-mesenchymal transition) in infiltrating breast carcinoma (IBC) and explore the role of them in invasion, metastasis and prognosis in IBC. METHODS: Expressions of MACC1, Snail and KISS-1 were examined by immunohistochemistry in 250 specimens of IBC and 80 specimens of normal breast tissues. Their clinicopathological features were analyzed, and their influence on patients' survival was identified. RESULTS: The positive rate of MACC1, Snail and KISS-1 in normal breast tissues and IBC tissues was 7.5%, 5.0%, 87.5% and 63.6%, 58.8%, 38.0%, respectively. And there was a significant difference between the IBC group and control group ( P<0.05). The positive expressions of MACC1, Snail and KISS-1 were significantly different in different TNM stages, lymph node metastasis, types and grades of tumor ( P<0.05). The survival time of positive KISS-1 group was significantly longer than that of negative group ( P<0.001); the survival time was significantly shorter in positive MACC1 group or Snail group than that of negative groups (both P<0.001). Cox regression analysis indicated that the positive expressions of MACC1, Snail and negative expression of KISS-1 were independent risk factors of IBC (P<0.05). CONCLUSIONS: Abnormal expression of MACC1, Snail and KISS-1 should be involved in the invasion and metastasis of IBC. The combined detection in the expressions of MACC1, Snail and KISS-1 at the early stage may play an important role in predicting the progression and prognosis of IBC.

Aberrant Expression of Markers of Cancer Stem Cells in Gastric Adenocarcinoma and their Relationship to Vasculogenic Mimicry.

BACKGROUND: Gastric cancer is the second leading cause of cancer-related death in Asia, and the majority type is gastric adenocarcinoma (GAC). Most GAC patients die of recurrence and metastasis. Cancer stem cells (CSCs) have been thought to be responsible for the initiation, development, metastasis, and ultimately recurrence of cancer. In this study, we aimed to investigate expression and clinical significance of CSCs markers, CD133 and Lgr5, and vasculogenic mimicry (VM) in primary GAC. MATERIALS AND METHODS: Specimens from 261 Chinese patients with follow-up were analyzed for CD133, Lgr5 protein expression and VM by immunohistochemical and histochemical staining. The Pearson Chi's square test was used to assess the associations among the positive staining of these markers and clinicopathological characteristics. Postoperative overall survival time was were studied by univariate and multivariate analyses. RESULTS: In GAC tissues, positive rates of 49.0%, 38.7%, and 26.8% were obtained for CD133, Lgr5, and VM, respectively. The mean score of microvessel density (MVD) was 21.7±11.1 in GAC tissues. There was a significantly difference between the positive and negative groups. There was a positive relationship between the VM, the expression of CD133 and Lgr5, and the score of MVD and the grades of tumor, lymph node metastasis, TNM stages (all p<0.05). The overall mean survival time of the patients with CD133, Lgr5, VM, and MVD (≥22) positive expression was lower than that of patients with negative expression. The score of MVD, positive expression of CD133 and VM were independent prognostic factors of GAC (p<0.05). CONCLUSIONS: VM, and expression of CD133, Lgr5, and the score of MVD are related to grades of tumor, lymph node metastasis, TNM stages, and overall mean survival time. It is suggested that CSCs and VM could play an important role in the evolution of GAC.