A Case of ALK-Positive Anaplastic Large Cell Lymphoma of the Male Breast.

Background: Primary breast lymphoma (PBL) is a very rare form of non-Hodgkin's lymphoma (NHL). A primary T-cell lymphoma in the breast with no previously identified lymphomatous lesions is an even rarer form of this malignancy. Case Presentation: A biopsy of a breast mass in a 60-year-old Caucasian man showed a morphologic-immunophenotypic profile with features characteristic of an ALK-positive (AKT+), anaplastic large cell lymphoma. Fluorescence in situ hybridization (FISH) analysis of fixed, paraffin-embedded tissue of this lesion was performed at our institution for IRF4/DUSP22 gene rearrangement. No rearrangement was detected. The patient presented with mutations in the following genes; BCOR_p.Q600X, DNMT3A_p.F609fs, NOTCH1_p.P2320fs, and IDH2_p.R140Q. However, the patient's consultation was complicated by the fact that he had been diagnosed with breast cancer at a local hospital and had come to our institution for further consultation. The histology findings were confirmed by immunohistochemistry and FISH. Computed tomography and positron emission tomography did not reveal nodules elsewhere in the body, which allowed the staging of the patient to be completed. However, although the patient had previously received the chemotherapy CCOP regimen (ie, cyclophosphamide, vincristine, prednisolone acetate) he did not go into remission in a timely manner and relapsed after six months, followed by a drastic deterioration in his condition after four months, resulting in his death in less than one month. Conclusion: This report of a male patient describes a case of a rare T-cell lymphoma of the breast that occurs considerably more frequently in female patients. The differential diagnosis of the histology of this tumor showed mutations that occur more often in lymphoblastic lymphoma or leukemia. This rare malignancy and associated mutations led to the death of this patient during treatment.

Multi-center study on predicting breast cancer lymph node status from core needle biopsy specimens using multi-modal and multi-instance deep learning.

The objective of our study is to develop a deep learning model based on clinicopathological data and digital pathological image of core needle biopsy specimens for predicting breast cancer lymph node metastasis. We collected 3701 patients from the Fourth Hospital of Hebei Medical University and 190 patients from four medical centers in Hebei Province. Integrating clinicopathological data and image features build multi-modal and multi-instance (MMMI) deep learning model to obtain the final prediction. For predicting with or without lymph node metastasis, the AUC was 0.770, 0.709, 0.809 based on the clinicopathological features, WSI and MMMI, respectively. For predicting four classification of lymph node status (no metastasis, isolated tumor cells (ITCs), micrometastasis, and macrometastasis), the prediction based on clinicopathological features, WSI and MMMI were compared. The AUC for no metastasis was 0.770, 0.709, 0.809, respectively; ITCs were 0.619, 0.531, 0.634, respectively; micrometastasis were 0.636, 0.617, 0.691, respectively; and macrometastasis were 0.748, 0.691, 0.758, respectively. The MMMI model achieved the highest prediction accuracy. For prediction of different molecular types of breast cancer, MMMI demonstrated a better prediction accuracy for any type of lymph node status, especially in the molecular type of triple negative breast cancer (TNBC). In the external validation sets, MMMI also showed better prediction accuracy in the four classification, with AUC of 0.725, 0.757, 0.525, and 0.708, respectively. Finally, we developed a breast cancer lymph node metastasis prediction model based on a MMMI model. Through all cases tests, the results showed that the overall prediction ability was high.

RT-qPCR is helpful to distinguish the clinicopathological features of HER2 immunohistochemistry 0 and 1.

The most commonly applied techniques to assess human epidermal growth factor receptor 2 (HER2) expression in breast cancer are immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). HER2 detection by reverse transcription quantitative polymerase chain reaction (RT-qPCR) can provide standardized, objective and automated assessment and reflect the HER2 expression continuity. Currently, there is lack of sufficient evidence to validate whether RT­qPCR technique is more appropriate for the detection of HER2 low expression, especially ultra-low expression. Here, we primarily utilized RT-qPCR to differentiate HER2 true negative, ultra-low and 1 +, and compare the clinicopathological features and prognosis between RT-qPCR and IHC. 136 breast cancer cases with HER2 0 or 1 + were collected, also included 21 cases with HER2 2 + FISH negative as well as 25 cases with HER2 positive during the same period for comparative analysis. Compared the mRNA levels based on IHC/FISH scores. The receiver operating characteristic (ROC) curve was utilized to determine the threshold for reclassification, and the clinicopathological characteristics and prognosis differences among IHC true negative, ultra-low and 1 + after re-classification by RT-qPCR were analyzed. The mRNA level significantly differed between the IHC 0 and 1 + groups (p < 0.001). The IHC 0 group was further divided into true negative and ultra-low, there was no statistically significant difference in mRNA levels between true negative and ultra-low groups, while the difference between ultra-low and 1 + mRNA levels was statistically significant (p < 0.001). After reclassification of IHC true negative, ultra-low and 1 + by RT-qPCR, there were statistically significant differences in histological grade, ER, PR and TILs expression. There was no significant difference between DFS and OS in the two classification methods. RT-qPCR classification aids in distinguishing clinicopathological characteristics and can serve as a supplementary technique for detecting HER2-low by IHC.

Expression and prognostic analysis of CLDN18 and Claudin18.2 in lung adenocarcinoma.

BACKGROUND: CLDN encodes a member of the claudin family. Claudin is a tight junction protein that is mainly involved in cell migration. Claudin family is of interest as a potential therapeutic target. Claudin18.2 is one of its important isoforms and is mainly expressed in the stomach. Its expression and prognosis in lung adenocarcinoma remain unknown. The aim of this study was to investigate the correlation between CLDN18 and claudin18.2 expression and prognosis in lung adenocarcinoma. METHODS: Two cohorts were introduced in this study: one from The Cancer Genome Atlas (TCGA) CLDN18 mRNA public data (TCGA-LUAD, N = 551); the other from 1079 cases of lung adenocarcinoma diagnosed at the Fourth Hospital of Hebei Medical University, China, with immunohistochemical (IHC) detection of claudin18.2 in tissue microarrays. the IHC-positive cases were again verified by fluorescence in situ hybridization (FISH). RESULTS: The mRNA expression of CLDN18 was significantly lower in lung adenocarcinoma tissues than in normal lung tissues (P < 0.05). Among 1079 Chinese lung adenocarcinoma cases, the overall positive rate of IHC for Claudin18.2 was 7.78% (84/1079). Among those positive for IHC, the positive rate of FISH was 11.9% (10/84), which accounted for 0.9% of the total number of cases (10/1079). To explore the best scoring scheme for Claudin 18.2, we used a four-group (IHC4) and two-group (IHC2) scoring method for evaluation. We found that IHC4 better explained Claudin 18.2 expression and helped us to find specific differences in clinical factors for weak, moderate and strong Claudin 18.2 expression. This difference was not discernible in the IHC2 score. By survival analysis, we found that Claudin 18.2 (IHC4) was able to stratify the prognosis of lung adenocarcinoma patients, with strongly positive patients having a better prognosis than the other subgroups (p < 0.05). We also found that patients with EGFR wild type or PD-L1 < 1% accompanied by strong positive claudin18.2 had a significantly better prognosis than other subgroups (P < 0.05). CONCLUSION: Claudin18.2 (IHC4) better reveals the clinical and prognostic characteristics of patients with lung adenocarcinoma. Patients with EGFR wild type and PD-L1 < 1% have a better prognosis and partially overlap with claudin18.2 expression, so claudin18.2 may also be an important biomarker for lung adenocarcinoma testing, which is particularly important for EGFR wild type and PD-L1 < 1%.

Highly expressed SLCO1B3 inhibits the occurrence and development of breast cancer and can be used as a clinical indicator of prognosis.

The role of organic anion transporting polypeptide 1B3 (SLCO1B3) in breast cancer is still controversial. The clinical immunohistochemical results showed that a greater proportion of patients with negative lymph nodes, AJCC stage I, and histological grade 1 (P < 0.05) was positively correlated with stronger expression of SLCO1B3, and DFS and OS were also increased significantly in these patients (P = 0.041, P = 0.001). Further subgroup analysis showed that DFS and OS were significantly enhanced with the increased expression of SLCO1B3 in the ER positive subgroup. The cellular function assay showed that the ability of cell proliferation, migration and invasion was significantly enhanced after knockdown of SLCO1B3 expression in breast cancer cell lines. In contrast, the ability of cell proliferation, migration and invasion was significantly reduced after overexpress the SLCO1B3 in breast cancer cell lines (P < 0.05). Overexpression or knockdown of SLCO1B3 had no effect on the apoptotic ability of breast cancer cells. High level of SLCO1B3 expression can inhibit the proliferation, invasion and migration of breast cancer cells, leading to better prognosis of patients. The role of SLCO1B3 in breast cancer may be related to estrogen. SLCO1B3 will become a potential biomarker for breast cancer diagnosis and prognosis assessment.

High expression of TCN1 is a negative prognostic biomarker and can predict neoadjuvant chemosensitivity of colon cancer.

Transcobalamin (TCN1) is a vitamin B12 (cobalamin)-binding protein that regulates cobalamin homeostasis. Recent studies and bioinformatic analyses have found that TCN1 is highly expressed in cancer tissues and is associated with tumour aggressiveness and poor prognosis. The present study aimed to detect TCN1 as a novel biomarker for prognosis and chemosensitivity of colon cancer. Next-generation sequencing showed that TCN1 was one of several upregulated mRNAs in colon cancer, which was verified by further bioinformatics analyses. Western blotting (n = 9) and quantitative real time polymerase chain reaction (qRT-PCR, n = 30) revealed that TCN1 was highly expressed in colon cancer tissues at both the protein and mRNA level. A total of 194 cases of colon cancer were examined by immunohistochemistry and revealed that TCN1 expression level was related to advanced stages (P < 0.005). Kaplan-Meier analysis verified that patients with lower TCN1 expression usually had longer overall survival (P = 0.008). In addition, TCN1 was highly expressed in pulmonary metastatic tumour tissues (n = 37, P = 0.025) and exhibited higher levels in right-sided colon cancer than in left-sided colon cancer (P = 0.029). TCN1 expression in specimens that had received neoadjuvant chemotherapy decreased compared with that in colonoscopy biopsy tissues (n = 42, P = 0.009). Further bioinformatics analyses verified that apoptosis pathways might have a role in high TCN1 expression. All the studies revealed that TCN1 expression in colon cancer was significantly associated with malignant biological behaviour. Therefore, TCN1 could be used as a novel biomarker for colon cancer aggressiveness and prognosis and might also be a potential biomarker for predicting neoadjuvant chemosensitivity.

The Effect of the Leptin and Leptin Receptor Expression on the Efficacy of Neoadjuvant Chemotherapy in Breast Cancer.

BACKGROUND The purpose of the present study was to evaluate the effect of leptin and leptin receptor (LEPR) expression on the efficacy of neoadjuvant chemotherapy in breast cancer. MATERIAL AND METHODS There were 325 breast cancer patients with complete data enrolled in this study. Patients were categorized into 3 groups: pathological complete response group, non-pathological complete response group, and progressive disease group. Immunohistochemistry was performed to determine leptin and its receptor LEPR expression levels that were compared among the 3 groups. RESULTS Compared with the non-pathological complete response group, patients in the pathological complete response group had increased leptin and LEPR expression, although the difference was not statistically significant (P=0.194, P=0.110). In addition, the expression of leptin and LEPR in the pathological complete response group was also higher than that in the progressive disease group, and the difference of LEPR expression was statistically significant (P=0.008) while the leptin expression was not (P=0.065). There were more HER2+ breast cancer patients in the pathological complete response group categorized into strong positive, and positive expression of leptin and LEPR compared with the progressive disease group (P<0.05). There were significant differences of leptin and LEPR expression among breast cancer patients under different molecular subtypes HER2+, HR+, and triple negative, in which the triple negative patients had the highest expression of leptin and LEPR. In addition, patients in the progressive disease group had high and low expression of leptin and LEPR: 13.25% versus 11.32% and 13.1% versus 10.42% respectively. CONCLUSIONS Overexpression of leptin and LEPR improved the therapeutic efficacy of neoadjuvant chemotherapy for patients with breast cancer, especially for those with HER2+ subtype. Overexpression of leptin and LEPR was distinct among the different molecular subtypes of breast cancer, suggesting a certain predictive value for breast cancer prognosis.

High expression of SDF-1 and VEGF is associated with poor prognosis in patients with synovial sarcomas.

Stromal cell-derived factor-1 (SDF-1) predicts poor clinical outcomes of certain types of cancer. Furthermore, vascular endothelial growth factor (VEGF) promotes the growth and metastasis of solid tumors. The aim of the present study was to examine the expression of SDF-1 and VEGF in patients with synovial sarcoma and to determine their expression is correlated with unfavorable outcomes. Levels of SDF-1 and VEGF proteins were evaluated in 54 patients with synovial sarcoma using immunohistochemical and immunofluorescence staining. Potential associations between the expression of SDF-1 and VEGF and various clinical parameters were analyzed using Pearson's χ2 test and the Spearman-rho test. Additionally, univariate and multivariate Cox regression analyses were used to identify potential prognostic factors, and the Kaplan-Meier method was used to analyze the overall survival rates of patients. Low SDF-1 and VEGF expression was detected in 20.4% (11/54) and 22.2% (12/54) of patients with synovial sarcoma; moderate expression was detected in 35.2% (19/54) and 37.0% (20/54) of patients and high expression was detected in 44.4% (24 of 54) and 40.7% (22 of 54) of patients, respectively. Levels of SDF-1 and VEGF proteins were significantly associated with histological grade (P<0.05), metastasis (P<0.05) and American Joint Committee on Cancer staging (P<0.05). In addition, levels of SDF-1 and VEGF expression were positively correlated with each other (P<0.001). Univariate analysis also indicated that VEGF expression was associated with shorter overall survival rates in (P<0.05), whereas multivariate analysis demonstrated that SDF-1 expression was associated with shorter patient survival rates (P<0.05). Finally, both SDF-1 and VEGF expression were associated with various characteristics of synovial sarcoma. Therefore, SDF-1 expression may be a potential independent prognostic indicator in patients with synovial sarcomas.

Evaluation of miR-21 and miR-375 as prognostic biomarkers in oesophageal cancer in high-risk areas in China.

MicroRNAs have been associated with prognosis in oesophageal cancer (EC), suggesting that miRNAs could play a role in guiding treatment decisions. The aim of this study was to evaluate the prognostic potential of miRNAs found to be associated with zinc deficiency in a geographical area with a high incidence of EC. miRNAs found to be associated with zinc deficiency were isolated from EC cell lines cultured with various Zn levels. The expression levels of the miRNAs were quantified using qRT-PCR. The potential prognostic value of the selected miRNAs was assessed in a cohort study of 88 patients from an area in China with a high incidence of EC. Correlations between miRNAs and patient characteristics were assessed using χ2 statistical tests or Fisher's exact test. A Cox proportional hazards model was used to assess the correlations between miRNAs and overall survival (OS). Forest plots were performed to evaluate the prognostic impact of the miRNAs examined in the present study in the Asian population. The expression levels of miR-21, miR-31, miR-93 and miR-375 were different when Zn levels were varied in EC cell lines, but only miR-21 and miR-375 were associated with patient characteristics and prognosis in patients with EC from an area of China with a high incidence of EC. The patients expressing high levels of miR-21 had poor OS (HR 2.15, 95% CI 1.16-3.97), whereas those with high levels of miR-375 had improved OS (HR 0.47, 95% CI 0.26-0.87).The patients with both a high level of miR-375 and a low level of miR-21 had significantly better outcomes. Forest plots based on an analysis of this Asian population indicated that a high level of miR-21 significantly predicted a shortened OS (HR 1.83, 95% CI 1.42-2.37), whereas a high level of miR-375 was significantly correlated with increased survival (HR 0.56, 95% CI 0.43-0.73). MiR-21 and miR-375 could be used as prognostic biomarkers in areas with a high incidence of EC, and combining these markers may results in a better effect.

Importance of SALL4 in the development and prognosis of hepatocellular carcinoma.

AIM: To detect the expression of sal-like protein 4 (SALL4) and to explore its relationship with clinicopathological characteristics and prognosis of hepatocellular carcinoma (HCC). METHODS: One hundred and twenty-six samples of HCC tissue, 44 of adjacent noncancerous cirrhotic tissue and 10 of liver hemangioma tissue, were obtained from patients who underwent hepatectomy for HCC at the Fourth Hospital of Hebei Medical University. None of the patients had received any form of treatment before the operation. After resection, all the tissues were fixed in 10% neutral formaldehyde and embedded in paraffin. Expression of SALL4 was detected by immunohistochemistry. Patients were followed up for postoperative survival until February 2014. The relationships between SALL4 expression level and clinicopathological data and prognosis of HCC were analyzed. RESULTS: SALL4 expression was negative in the 10 samples of tissue from liver hemangioma, was weakly positive in the two samples from adjacent noncancerous cirrhotic tissue, and positive in 58 samples of HCC tissues. The differences were statistically significant (P < 0.05). Expression of SALL4 was higher in patients with higher α-fetoprotein (AFP) levels, portal vein tumor thrombus, and later clinical stage based on the Barcelona Clinic Liver Cancer classification (P < 0.05). Among patients with negative expression, weakly positive expression, positive expression, and strongly positive expression of SALL4, the median survival time was 39, 25, 23, and 9 mo, respectively (P < 0.001). When both AFP and SALL4 were detected, patients who were negative for both AFP and SALL4, SALL4-positive only, AFP-positive only, and positive for both AFP and SALL4, had a median survival time of 41, 38, 31, and 12 mo, respectively (P < 0.001). CONCLUSION: Expression of SALL4 is relevant to the prognosis of HCC patients. Patients with higher expression levels of SALL4 and AFP have worse prognosis.

Apolipoproteins as Differentiating and Predictive Markers for Assessing Clinical Outcomes in Patients with Small Cell Lung Cancer.

PURPOSE: The present study aimed to investigate the value of apolipoproteins, including ApoA-1, ApoC-III, and ApoE, in patients with small cell lung cancer (SCLC) as potential biomarkers for diagnosis, prognosis, and cancer progression. MATERIALS AND METHODS: Lung samples were collected from 89 patients with SCLC. Nineteen lung samples from non-small cell lung cancer (NSCLC) patients and 12 normal lung tissues were used as controls. Expression profiles of ApoA-1, ApoC-III, and ApoE in different samples were examined using immunohistochemical methods, and the expression levels were correlated with cancer types, treatment, and outcomes using chi-square and Mann-Whitney tests. RESULTS: Expression of ApoA-1 and ApoC-III in SCLC was significantly different, compared with that in NSCLC and normal lung tissues, and was correlated with recurrence of SCLC. Patients undergoing neoadjuvant chemotherapy before surgery showed significantly reduced expression of ApoA-1 and increased expression of ApoC-III and ApoE. Nevertheless, the expression levels of ApoA-1, ApoC-III, and ApoE were not correlated with SCLC staging. CONCLUSION: ApoA-1 and ApoC-III may be used as differentiating and predictive markers for SCLC. ApoA-1, ApoC-III, and ApoE may be used to monitor the efficacy of chemotherapy.

Single nucleotide polymorphisms in the mitochondrial displacement loop region and outcome of malignant fibrous histiocytoma.

PURPOSE: Single nucleotide polymorphisms (SNPs) in the mitochondrial DNA displacement-loop (D-loop) region have been reported to be associated with cancer risk and disease outcome in several types of cancer. In this study, we investigated whether the SNPs in mitochondrial D-loop were associated with the outcome of malignant fibrous histiocytoma (MFH). EXPERIMENTAL DESIGN: The D-loop region of mtDNA was sequenced for 80 MFH patients. The 3 years survival curve were calculated with the Kaplan-Meier method and compared by the log-rank test at each SNP site, a multivariate survival analysis was also performed with the Cox proportional hazards method. RESULTS: The SNP sites of nucleotides 152T/C, 16,390G/A, 16,290C/T, 16,304T/C and the AC deletion at sites 523 and 524 were identified for prediction of post-operational survival by the log-rank test. In an overall multivariate analysis, the 16,290 and 16,390 alleles were identified as independent predictors of MFH outcome. The length of survival for patients with the rare allele 16,390A genotype was significantly shorter than that for patients with the frequent allele 16,390Gat the site 16,390. The same was seen for the rare allele 16,290T genotype when compared with matched allele 16,290C at the site 16,290 in MFH patients. CONCLUSIONS: These results suggested that SNPs in the D-loop are independent prognostic markers for patients with MFH. The analysis of genetic polymorphisms in the D-loop can help identify patient subgroups at higher risk of a poor disease outcome.

Identification of sequence polymorphisms in the D-loop region of mitochondrial DNA as risk biomarker for liposarcoma.

Single nucleotide polymorphisms (SNPs) in the Displacement-loop (D-loop) region of mitochondrial DNA have been reported to be associated with cancer risk in various types of cancer. To assess the frequency of D-loop SNPs in a large series of liposarcoma and establish correlations with cancer risk, we sequenced the D-loop of 82 liposarcoma patients and analyzed their use as predictive biomarkers for liposarcoma risk. The minor alleles of nucleotides 73G, 523-524del, 16,290T, 16,319A, 16,356C were associated with an increased risk for liposarcoma patients, whereas the insertion of C at the site 315 (located within the D310) were associated with a decreased risk for liposarcoma patients. These results suggest that SNPs in the mitochondrial D-loop should be considered as a biomarker which may be useful for the early detection of liposarcoma in individuals at risk of this cancer.

Preventive effect of hydrazinocurcumin on carcinogenesis of diethylnitrosamine-induced hepatocarcinoma in male SD rats.

The purpose of the present study was to evaluate the preventive effects of hydrazinocurcumin (HZC) on diethylnitrosamine (DEN)-induced hepatocarcinogenesis in a male Sprague Dawley (SD) rat model. One hundred and twenty male SD rats used in this study were divided into six groups. Those receiving DEN with curcumin (CUR) or HZC were studied compared with the DEN-alone group. The study demonstrated that DEN induced severe histological and immunohistochemical changes in liver tissues, significantly increasing the levels of liver marker enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyltransferase (GGT) and total bilirubin level (TBL)). The hepatocarcinoma incidences were 100.0%, 36.7% and 20.0% in the DEN-alone, DEN-CUR and DEN-HZC groups, respectively. Although macroscopic and microscopic features suggested that both CUR and HZC were effective in inhibiting DEN- induced hepatocarcinogenesis, HZC was exerted a stronger influence. Immunohistochemical analysis with PCNA demonstrated significantly differences among the groups (all P < 0.05). Taken together, the results suggested application of CUR and HZC could prevent the occurrence of carcinogenesis and HZC may be a more potent compound for prevention of DEN-induced hepatocarcinogenesis in rats than CUR.

Sirtuin-3 (SIRT3) expression is associated with overall survival in esophageal cancer.

Sirtuin-3 (SIRT3) was immunostained in 94 samples of esophageal cancer tissues and semiquantified using the HSCORE method to evaluate the predictive value of SIRT3 expression levels on esophageal cancer outcome. The relationship between SIRT3 expression and the 5-year survival rate of postoperational esophageal cancer patients was assessed with the Kaplan-Meier method. High expression of SIRT3 is associated with a shorter survival time in esophageal cancer patients, as shown by the log-rank test (P = .007), and the level of SIRT3 expression was identified as an independent predictor for esophageal cancer outcome using Cox proportional hazards model analysis (relative risk, 2.061; 95% confidence interval, 1.050-4.046; P = .036). SIRT3 expression was associated with esophageal cancer outcome. The analysis of SIRT3 levels can help in the identification of patient subgroups that are at high risk for poor disease outcomes.

The effect of childbirth on carcinogenesis of DMBA-induced breast cancer in female SD rats.

Many epidemiologic and clinical studies have indicated that the frequency of breast cancer was lower in parous women than in nulliparous women. Moreover, the incidence of breast cancer has been reported to be lower in women with early childbirth than in women with late childbirth. To verify the effect of childbirth and the age at first childbirth on carcinogenesis and progression of breast cancer, we induced breast cancer by 7,12-dimethylbenanthracene (DMBA) in 120 female Sprague-Dawley (SD) rats, and divided them into control or experimental (DMBA-treated) nulliparous, early childbirth, and late childbirth groups to observe the incidence, latency, and size of breast cancer. Argyrophilic nucleolar organizer regions (AgNOR) count and the expression of C-erbB-2, proliferating cell nuclear antigen (PCNA), Ki-67, and minichromosome maintenance protein 2 (MCM2) in breast cancer tissues were detected by immunohistochemistry. The breast cancer incidences were 95.0%, 16.7%, and 58.8% in the experimental nulliparous, early childbirth, and late childbirth groups, respectively (all P < 0.05). Between any two of these groups, the latency was significantly different, but tumor size was similar. AgNOR count and the expression of C-erbB-2, PCNA, Ki-67, and MCM2 were significantly higher in the experimental nulliparous group than in the experimental early or late childbirth groups (P < 0.05), but no significant differences were observed between the latter two groups. Taken together, the results suggest that childbirth, especially early childbirth, can reduce the incidence and postpone the onset of DMBA-induced breast cancer.

Expression of vascular endothelial growth factor-C and the relationship between lymphangiogenesis and lymphatic metastasis in colorectal cancer.

AIM: To investigate the expression of vascular endothelial growth factor-C (VEGF-C) and the relationship between VEGF-C and lymphangiogenesis, lymph node metastasis in colorectal cancer. METHODS: Fifty six cases of colorectal cancer were selected randomly. Expression of VEGF-C was detected by immunohistochemistry, and lymphatic vessels were stained by enzyme histochemical method. RESULTS: VEGF-C expression was found in 66.7% (37/56) patients. In VEGF-C positive and negative patients, the lymphatic vessel density was 25.16+/-7.52 and 17.14+/-7.22, respectively (P<0.05). The rate of lymph node metastasis in VEGF-C positive patients (81.1%) was significantly higher than that in the negative group (42.1%). CONCLUSION: VEGF-C expression may induce lymphangiogenesis in colorectal cancer, as a result, tumor cells can entry the lymphatic vessels easily. VEGF-C may serve as a useful prognotic factor in colorectal carcinoma.

[Flow cytometric detection and significance of four cyclins in esophageal cancer].

OBJECTIVE: To study the expression and significance of cyclin E, cyclin D1, CDK4 and p27 protein in esophageal squamous cell cancer (ESCC) and their correlation with tumor differentiation and lymph node metastasis. METHODS: Expressions of cyclin E, cyclin D1, CDK4 and p27 protein in 65 patients with ESCC were quantitatively detected by flow cytometry. RESULTS: The expressions of cyclin E, cyclin D1, CDK4 in poorly-differentiated ESCC were higher than those in well-differentiated ESCC (P = 0.0275, 0.0001, 0.0174). The expression of p27 in poorly-differentiated ESCC was lower than that in well-differentiated ESCC (P = 0.0042). There was positive correlation between cyclin E and cyclin D1, cyclin D1 and CDK4, but negative correlation between cyclin D1 and p27. The expressions of all four proteins were not correlated with lymph node metastasis. CONCLUSION: The expressions of cyclin E, cyclin D1, CDK4 and p27 are closely related to tumor differentiation of ESCC. An imbalance between positive and negative control of cell cycling might be critical in the carcinogenesis of esophageal squamous cell cancer.