Acyl-CoA thioesterase 8 is a specific protein related to nodal metastasis and prognosis of lung adenocarcinoma

Metastasis is a major cause of cancer recurrence or death. This study attempted to quantitatively identify different proteins in metastatic lung adenocarcinoma. The N/T quotient [number of metastatic lymph nodes (n)/tumor diameter (cm)] was used to select samples with an extreme metastatic phenotype. Among the six fresh frozen lung adenocarcinoma specimens, the three showing the highest N/T quotient represented the metastatic group, and others with the greatest tumor diameters without metastasis represented the non-metastatic group. After 2-dimensional electrophoresis, the significantly different protein spots were selected by image analysis and analyzed with MALDI-TOF mass spectrometry. Acyl-CoA thioesterase 8 isoform c (ACOT8) was one of most overexpressed proteins in the metastatic group, and it was validated by Western blot and immunohistochemical staining on 108 paraffin-embedded tumor samples. High ACOT8 expression was correlated with lymph node metastasis (p = 0.002), recurrence (p = 0.034), predominant histologic subtypes (p = 0.007), and higher stage (p = 0.005). In multivariate analysis, high ACOT8 expression was significantly associated with increased risks of lymph node metastasis (p = 0.009) and cancer-related death (p = 0.030), independent of clinical factors. ACOT8 may be a candidate prognostic biomarker and therapeutic target of lung adenocarcinoma.     

Effect of BRCA1 immunohistochemical localizations on prognosis of patients with sporadic breast carcinomas

Our purpose was to investigate the expression pattern of BRCA1 protein in sporadic breast carcinomas, as well as the clinicopathological and prognostic value of its subcellular localizations. Immunohistochemistry was performed on paraffin embedded tissue specimens from 111 sporadic, invasive breast carcinomas to detect the expression of the proteins BRCA1, ER, PR, erbB2, p53 and Ki67. BRCA1 protein was detected in the nuclei and the cytoplasm of the tumor cells. Nuclear BRCA1 immunoreactivity showed no relation with the classic clinicopathological markers and the expression of cerbB2, p53 and Ki67. Reduced expression of nuclear BRCA1 protein was found to exert an independent favorable impact on both the overall and relapse-free (RF) survival of the patients (p = 0.019 and p = 0.043, respectively). Cytoplasmic BRCA1 was associated with none of the classic histomorphological indices, except from the lymph node metastasis, with which its relation was found to be inverse (p = 0.05), prolonging the RF survival of the patients (p = 0.05). Our findings suggest that BRCA1 protein depicts different prognostic significance, according to its subcellular distribution. Nuclear detection of the protein was associated with a worse prognosis, while the cytoplasmic one was related to fewer recurrences as a result of fewer lymph node metastases.     

Prognostic importance of PAI-1 in node negative breast cancer patients--results after 10 years of follow up

The serine protease urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) play key roles in the proteolytic cascade involved in physiological and pathological degradation of the extracellular matrix.The aim of this study was to determine the prognostic importance of PAI-1 expression in tumor cells in node-negative breast cancer patients that did not receive adjuvant chemotherapy. We used immunohistochemistry (IHC) as a detection method. The study retrospectively included 133 ductal invasive breast cancer patients from the Clinical Hospital Center Zagreb, Croatia, surgically treated in a two-year interval (1998-1999) with 10 years of follow up.The Cox proportional hazard regression test with stepwise variable selection was used to calculate the relative effect of investigated data on patients’ prognosis. Univariate analysis showed that all investigated factors, such as lymph node involvement (p = 0.025), tumor grade (p < 0.001), estrogen receptor status (p = 0.011), vascular invasion (p = 0.001), HER2 overexpression (p < 0.001), and proliferative index (p < 0.001), had a statistically significant influence on patients’ OS. Multivariate statistical analysis showed that only HER-2 (p < 0.001) can be considered an independent, statistically significant poor prognostic factor.In patients with negative lymph nodes that did not receive adjuvant chemotherapy, we found a significant correlation in overall survival (p = 0.009), which is favorable for PAI-1 negative tumors.In conclusion, it seems that PAI-1 in primary breast cancer tissue correlates with disease aggressiveness and has a strong prognostic impact on primary breast cancer, and is a strong prognostic factor for node-negative patients that did not receive chemotherapy.     

Obesity is associated with a poorer prognosis in women with hormone receptor positive breast cancer

Objective

Whether moderate to severe obesity (body mass index (BMI) ≥ 30 to <40 kg/m²) contributes to breast cancer recurrence and mortality remains uncertain.

Subjects and methods

1199 women, recruited within 12 months of their diagnosis of hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2−) invasive breast cancer completed an enrolment questionnaire and an annual follow-up questionnaire every 12 months for another 5 years. The impact of obesity on time to either local or distant recurrence or new breast cancer, or death due to breast cancer was determined by Cox regression. Women in the most extreme categories of BMI (<18.5 and ≥40) were excluded from the analysis.

Results

Of the 1155 included women, mean age, 58.4 ± 11.6 years, 53.8% had Stage 1 disease and 88.9% received oral adjuvant endocrine therapy (OAET) within 2 years of diagnosis. The likelihood of an event was significantly associated with moderate to severe obesity (HR = 1.71, 95%CI, 1.12–2.62, p = 0.014), disease beyond Stage 1 (HR = 2.87, 95% CI 1.73–4.75, p < 0.001), OAET (HR = 0.26, 95%CI 0.14–0.46, p < 0.001), mastectomy (HR = 3.28, 95%CI 1.98–5.44, p < 0.001) and radiotherapy (HR = 2.12, 95%CI 1.24–3.63, p = 0.006). For Stage 1 disease, only moderate to severe obesity (HR 3.23, 95%CI 1.48–7.03, p = 0.003) and OAET use (HR 0.41, 95%CI 0.17–0.98, p = 0.046) were significantly associated with an event.

Conclusion

Moderate to severe obesity is associated with a poorer invasive breast cancer prognosis; this is also true for women with Stage 1 disease, and is independent of age and treatment.     

Osteopontin is associated with decreased apoptosis and αv integrin expression in lung adenocarcinoma

Osteopontin (OPN) is a glycoprotein involved in invasion, progression and metastasis of many carcinomas. It contains several functional domains including binding sites for αv integrins, cell surface molecules playing a major role in mediating cell migration and adhesion. The aim of the study was to evaluate the expression of osteopontin in human non-small cell lung cancer (NSCLC) and to determine its possible prognostic significance as well as relation to apoptosis and αv integrin expression. We analyzed 111 surgically resected NSCLC for immunohistochemical expression of OPN and αv integrin. OPN expression was compared to apoptotic rate and clinicopathological parameters such as tumor size, histological grade, lymph node status, pT, and TNM stage. Apoptotic rate was measured by TUNEL staining method. OPN expression in NSCLC was significantly higher in lung adenocarcinomas (AC) then in squamous cell carcinomas (p < 0.001). There was no correlation between OPN expression and clinicopathological parameters. The level of OPN expression in AC was associated with decreased apoptotic activity of tumor cells (p = 0.006), and correlated with αv integrin expression (p = 0.048), particularly in low stage tumors (p = 0.013). Prolonged tumor cell survival in lung AC due to OPN and αv integrin overexpression may have an impact on tumor progression and resistance to therapy.     

Association between the HLA-G molecule and lymph node metastasis in papillary thyroid cancer

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer and can present as lymph node metastasis in 30 to 65% of cases when initially diagnosed. High frequency recurrence, distant metastasis and treatment resistance can be found in cases of PTC so early diagnosis and treatment are critical for improved prognosis and better survival rates. The characterization of new biomarkers has proved useful for the diagnosis and follow-up of these patients. HLA-G is a non-classical HLA class I molecule whose expression in cancer cells has been associated with tumor evasion of immune response. Therefore, the aim of this study was to investigate the HLA-G expression and its clinical significance in PTC. Paraffin-embedded thyroid biopsies of 70 PTC patients (40 of whom had presented with metastasis) were evaluated. HLA-G-staining was observed in tumor cells in PTC, and the HLA-G expression was significantly associated with an increased occurrence of lymph node metastasis (p = 0.0006) and capsular invasion (p = 0.02). This preliminary data shows the HLA-G expression in thyroid carcinoma specimens for the first time and suggests that this expression could impair efficient anti-tumor immunity in PTC. This would indicate that HLA-G could have an independent prognostic value in PTC, principally for tumor recurrence.     

Expression of HAb18G/CD147 and its localization correlate with the progression and poor prognosis of non-small cell lung cancer

This study was designed to investigate the association of HAb18G/CD147 expression and localization with clinicopathological parameters and prognosis in NSCLC. Two hundred and eight (208) specimens of surgically resected NSCLC were stained by immunohistochemistry utilizing mouse anti-human HAb18G/CD147 monoclonal antibody. High levels of HAb18G/CD147 expression were associated with male gender, smoking history, tumor position, distant metastasis status, and clinical stage (p < 0.05) in squamous cell carcinoma. In adenocarcinomas, HAb18G/CD147 expression was associated with male gender, tumor diameter, differentiation, lymph node status, distant metastasis status, and clinical stage (p < 0.05). HAb18G/CD147 expression with higher PU was predominantly localized in the tumor cell membranes rather than in cytoplasms. In squamous cell carcinomas, membranous localization of HAb18G/CD147 was linked to distant metastasis status and TNM stage (p < 0.05). Cytoplasmic localization of HAb18G/CD147 was associated with male gender and smoking history. In adenocarcinomas, membranous localization of HAb18G/CD147 correlated with tumor diameter, differentiation and distant metastasis (p < 0.05). Univariate analysis indicated that patients with high HAb18G/CD147 expression and membranous localization predicted poor prognosis in both squamous cell carcinomas and adenocarcinomas. Multivariate analysis showed that lymph node status (HR = 1.762, 95%CI 1.105–2.811, p = 0.017), distant metastasis status (HR = 3.789, 95%CI 2.196–6.539, p = 0.000), expression (HR = 6.632, 95%CI 2.457–17.904, p = 0.000), and localization (HR = 0.520, 95%CI 0.341–0.794, p = 0.002) were good or excellent independent predictors of patient survival. HAb18G/CD147 is a biomarker characterizing progression and survival of NSCLC. More importantly, its cellular localizations should be considered in the analysis of clinicopathological characteristics and prognostic factors in NSCLC.     

Expression and prognostic relevance of centromere protein A in primary osteosarcoma

Centromere protein A (CENP-A) is one of the fundamental components of the human active kinetochore and plays important roles in cell-cycle regulation, cell survival, and genetic stability. The aim of the present study was to explore the expression and prognostic significance of CENP-A in osteosarcoma. The results of real-time quantitative PCR and Western blotting analysis revealed an enhanced expression of CENP-A in osteosarcomas relative to adjacent non-tumorous bone tissues at both mRNA and protein levels. Immunohistochemically, 72 of the 123 osteosarcoma specimens (58.5%) had high expression of CENP-A. CENP-A overexpression was significantly correlated with tumor size (P = 0.002), poor response to neoadjuvant chemotherapy (P = 0.016), local recurrence/lung metastasis (P = 0.001), high Ki-67 index (P = 0.004), and P53 positivity (P = 0.005). Median overall and recurrence-free survival time was significantly shorter in patients with high-CENP-A osteosarcomas than in those with low-CENP-A osteosarcomas. Multivariate analysis identified CENP-A as an independent poor prognostic factor for osteosarcoma. In conclusion, our results demonstrate that elevated CENP-A expression is significantly associated with osteosarcoma progression and has an independent prognostic value in predicting overall and recurrence-free survival for patients with osteosarcoma.     

Serum tissue polypeptide-specific antigen is an independent predictor in breast cancer

Tissue polypeptide-specific antigen (TPS) is a tumor proliferative marker associated with cytokeratin 18. The aim of the study was to investigate the potential relationship between the preoperative serum TPS levels and the outcome in Chinese breast cancer patients. 975 consecutive female patients, affected by invasive breast cancer under investigation from January 2005 to December 2011, had their TPS levels measured with a one-step solid phase radiometric sandwich assay detecting the M3 epitope on cytokeratin 18 fragments. The cut-off value was 80 U/L. The average age diagnosed with breast cancer was 48, ranging from 23 to 71. About 19% (185) patients displayed an elevated preoperative TPS level (>80 U/L) associated with older age (>45), advanced cancer stage, larger tumor size (>2 cm), axillary lymph node metastasis, negative progesterone receptor status, and positive HER2 status. In addition, preoperative TPS levels were also significantly connected with recurrence (p < 0.05), particularly distant metastasis and visceral metastasis. The mean preoperative TPS level was 68.4 ± 116.43 U/L (range 0–1839 U/L). In multivariate analysis, high preoperative TPS level was recognized as an independent prognostic factor for disease-free survival (p < 0.001 and overall survival (p = 0.023). From these results we conclude that the serum preoperative TPS level may be a valuable and independent marker for breast cancer.     

Evaluation of MMP2 and Caspase-3 expression in 107 cases of papillary thyroid carcinoma and its association with prognostic factors

Papillary thyroid carcinoma (PTC), including its variants and widely varying behavior, constitutes about 80% of all thyroid malignancies. Increased knowledge regarding molecular alterations has led to attempts to identify diagnostic or prognostic factors for a reliable preoperative approach to the classification of patients according to risk of recurrence. In this study, 107 cases of PTC with known histological properties, including vascular or capsular invasion, were assessed for expression of MMP2 and Caspase-3 using immunohistochemistry. Considering 10% as a cutoff to discriminate cases with invasive behavior from the non-invasive group, there was no relationship between expression of MMP2 or Caspase-3 in tumor cells and the presence of capsular invasion (p = 0.45 and 0.64, respectively), as well as for the expression of Caspase-3 and vascular invasion (p = 0.43). In case of MMP2, a borderline correlation was found between the positive reaction of tumor cells with the presence of vascular invasion (p = 0.05). So the evaluation of MMP2 in thyroid PTC appears to be of some benefit to the prediction of tumor behavior while Caspase-3 as a marker of prediction seems to be of no use.     

Gankyrin is frequently overexpressed in breast cancer and is associated with ErbB2 expression

Gankyrin is a subunit of the 26S proteasome, and has been known to degrade p53 and retinoblastoma protein and promote the tumorigenicity and metastasis in some malignancies. However, the role of gankyrin in breast cancer has not been explored. In this study, we investigated the expression of gankyrin in breast cancer and evaluated its effect on breast cancer. Representative cancer tissues including normal breasts from 60 patients with breast cancer were stained immunohistochemically for gankyrin, estrogen receptor, progesterone receptor, and ErbB2. We evaluated the relationship between gankyrin expression and clinicopathologic parameters or prognostic markers. We also attempted to clarify the mechanism of gankyrin involved in breast carcinogenesis by using MCF7 breast cancer cells. Gankyrin was weakly expressed in normal breast epithelial cells, however, tumor regions of 37/60 (61.7%) cases showed an overexpression of gankyrin. Gankyrin overexpression was associated with extensive intraductal carcinoma (p = 0.014) and ErbB2 positivity (p = 0.031) in invasive ductal carcinoma. In MCF7 breast cancer cells, downregulation of gankyrin was associated with a reduction of cell proliferation and tumorigenicity. In conclusion, gankyrin was identified in normal breasts and overexpressed in invasive breast cancers. The overexpression of gankyrin was associated with extensive intraductal carcinoma and ErbB2 expression in breast cancer.     

Notch3 signaling is associated with MUC5AC expression and favorable prognosis in patients with small intestinal adenocarcinomas

Background

Notch signaling plays diverse roles not only in physiologic processes, including development and differentiation but also in tumorigenesis, either as a tumor promoter or suppressor depending on the cellular context, level of expression and cross-talk with other signaling pathways. In this study we investigated the expression of Notch3 and MUC proteins and their clinicopathological significance in small intestinal adenocarcinoma (SIAC).

Methods

Surgically resected 191 SIACs and their clinical data were collected. Immunohistochemistry for Notch3, MUC2, MUC5AC, and MUC6 using tissue microarrays from formalin-fixed paraffin-embedded normal and matched tumor tissues was performed.

Results

Notch3 expression was found in 52 (29.9%) cases of the tumors. MUC2, MUC5AC, and MUC6 were expressed in 52 (27.5%), 51 (31.9%), and 42 (22.0%) cases of the tumor, respectively. Notch3 expression was correlated with the absence of lymphovascular invasion (p = 0.009), lower T stage (p = 0.038), and histological subtype of tubular adenocarcinoma (p = 0.01), respectively. MUC2 was correlated with large tumor size (p = 0.013) and mucinous and signet ring cell adenocarcinomas (p = 0.01). MUC5A was correlated with proximal tumor location (p < 0.0001) and tumor differentiation (p = 0.027). MUC6 was correlated with proximal tumor location (p < 0.0001) and lower pT stage (p = 0.009), and absence of lymphovascular invasion, respectively. A significant correlation was noted between Notch3 and MUC5AC expression (p = 0.019). Notch3 expression was a relatively favorable prognostic factor in SIACs by univariate (p = 0.05) and multivariate analysis (p = 0.08, Cox Hazard ratio 0.841).

Conclusion

Our findings indicate that Notch3 signaling, associated with MUC5AC expression, could be a more favorable prognostic factor in SIACs.     

Circulating estradiol defines the tumor phenotype in menopausal breast cancer patients

Objective

To correlate circulating hormone levels with the clinical and biological features of the tumors in menopausal breast cancer patients.

Design

Circulating hormone levels were measured in 161 previously untreated menopausal breast cancer patients within 72 h of their planned surgery. The obtained hormone levels were correlated with tumor size, histological and nuclear grade, histological score, axillary nodal status, DNA-ploidy and Ki67-, c-erb-B2-, p53, Bax-, VEGF- and Nup88-expression.

Results

The only statistically significant correlations found between circulating hormone levels and all tested variables were an inverse one between estradiol and the expression of the apoptosis-associated Bax gene (p = 0.009), and again an inverse correlation between estradiol and the expression of c-erb-B2 (p = 0.04). When comparing hormone levels with each other, a significant correlation between estradiol and progesterone (p < 0.0001), an inverse one between estradiol and FSH (p = 0.04) and a direct one between LH and prolactin (p = 0.001) were found.

Conclusion

Higher circulating estradiol levels in postmenopausal breast cancer patients are associated with molecular features usually defining a biologically less aggressive tumor phenotype.     

Trends in prostatic adenocarcinoma tumor volume by visual estimation in prostatectomy specimens

We retrospectively reviewed 1792 consecutive radical prostatectomies (RP) from 2003 to 2006 at a single institution to establish tumor volume reference values, to determine current trends in visually estimated prostate adenocarcinoma tumor volume, and to characterize cases with no residual cancer on RP. Tumor volumes were recorded and subsequently stratified as very low, 0–1%; low, 1.1–10%; intermediate, 10.1–20%; high, 20.1–50%; and very high, >50%, with incidences of 11.7%, 52.1%, 21.5%, 13.2%, and 1.5%, respectively. The incidence of very low volume tumors increased within the time period (p = 0.04). Seminal vesicle involvement was detected in 5.0% of cases and lymph node metastasis occurred in 1.4%. Volume categories statistically correlated with seminal vesicle invasion (p = 0) and lymph nodes metastases (p = 0). Eleven cases of no residual cancer (0.6%) were identified with a non-statically significant increase during the study (p = 0.07). The rising incidence of very low volume tumors should be considered by clinicians when discussing treatment options with patients. A discrete tumor volume should be provided for RP specimens as it may be an important prognostic factor.     

Significantly upregulated TACSTD2 and Cyclin D1 correlate with poor prognosis of invasive ductal breast cancer

The tumor-associated calcium signal transducer 2 (TACSTD2) gene has been reported to be highly expressed in many types of human epithelial cancers, and is associated with tumor metastasis and poor prognosis. The aims of the present investigation were to analyze the TACSTD2 and Cyclin D1 expression at the mRNA and protein levels and to assess its prognostic significance in invasive ductal breast cancer (IDC). The expressions of TACSTD2 and Cyclin D1 in IDC tissues were consistently higher than those in the tumor-adjacent non-malignant tissues by a one-step real-time polymerase chain reaction and immunohistochemistry (P < 0.001 and P = 0.023, respectively). The statistical analysis of clinicopathologic characteristics and immunohistochemistry by the χ² test showed that the high expression of TACSTD2 in IDC was correlated to histological grade (P = 0.023), P53 status (P = 0.042), Cyclin D1 status (P < 0.001), lymph node metastasis (P < 0.001), distant metastasis (P = 0.004) and TNM staging (P < 0.001). Kaplan–Meier survival and Cox regression analyses were performed to evaluate the prognosis of IDC. These analyses also showed that a high TACSTD2 expression (P = 0.003), a high Cyclin D1 expression (P = 0.041), and lymph node metastasis (P = 0.006) were independent prognosis factors. Collectively, our studies demonstrated that the high expression of TACSTD2 correlates with a poor prognosis in IDC.     

Glutathione transferase pi (GSTpi) expression in breast cancer: an immunohistochemical and molecular study

Breast cancer is the most frequent cancer in women worldwide. Prognostic markers are important for diagnosis, allowing therapeutic strategies to be defined more efficiently. The expression of the glutathione S-transferase pi isoenzyme (GSTpi) in tumor cells has been evaluated as a predictor of prognosis and in response to cytotoxic treatments. Its immunoexpression was assessed in 63 women diagnosed with invasive ductal carcinoma in a retrospective study. The results were statistically correlated with clinicopathological parameters of patients. The results showed that high GSTpi expression was related to p53-positive tumors, grade III histology, large tumor size and death (p < 0.05). The 37 patients who received adjuvant treatment, checked separately, showed high expression of GSTpi in relation to local recurrence, metastasis and death (p < 0.05). In addition, high levels of GSTpi expression were significantly associated with a shorter overall survival (p < 0.05). To confirm this suspicion, GSTpi gene expression was checked by Real-time PCR in neoplastic mammary cells cultured and subjected to treatment with doxorubicin. Our results suggest that high levels of GSTpi may be related to the development of resistance to chemotherapy in these tumors, the response of these tumors to treatment and the clinical course of the patients involved.     

Immunohistochemical COX-2 overexpression correlates with HER-2/neu overexpression in invasive breast carcinomas: a pilot study

Cyclooxygenase-2 (COX-2) is a prostaglandin synthase that catalyzes the synthesis of prostaglandin G2 and H2. It has been shown that COX-2 plays an important role in tumorigenesis of different tumor types and it is thought to take part in breast carcinogenesis. In the present study, we aimed to investigate the relationship of immunohistochemical COX-2 expression with clinicopathological parameters, including HER-2/neu overexpression in invasive breast carcinoma (IBC).Our study population comprised 10 normal breasts, 25 ductal carcinomas in situ (DCIS), and 51 invasive breast carcinomas. Immunohistochemical overexpressions of COX-2 and HER-2/neu were investigated in sections of formalin-fixed, paraffin-embedded blocks by 3 observers.In normal breast, DCIS and IBC, the COX-2 overexpression rate was 0%, 84%, and 58.8%, respectively. In IBC, COX-2 overexpression had a significant relationship with HER-2/neu overexpression (p = 0.026) and a high histological grade (p = 0.026). COX-2 expression in both DCIS (n = 25) and IBC (n = 51) was significantly higher than in normal breast tissue (p < 0.0001). In addition, the COX-2 expression rate was significantly higher in DCIS than in IBC (p = 0.042).Our results indicated that COX-2 overexpression correlates with aggressive phenotypic features, such as HER-2/neu overexpression and high histological grade in IBC. Increased expression of COX-2 in both DCIS and IBC in comparison to normal breast could indicate a role in breast carcinogenesis. COX-2 overexpression may provide a clinically useful biomarker for estimating tumor aggressiveness.     

Significance of galectins-1, -3, -4 and -7 in the progression of squamous cell carcinoma of the tongue

The aim of this study was to analyze the immunohistochemical expression of galectins-1, -3, -4, and -7 in 65 cases of squamous cell carcinoma of the tongue and to correlate this expression with clinical (disease outcome, metastasis, and clinical stage) and morphological parameters (histological grade of malignancy). Clinical data were obtained from the patient records. The histological grading system of malignancy proposed by Bryne (1998) [9] was used for the analysis of morphological parameters. The results were analyzed statistically by χ² test (p < 0.05). Galectin-1 expression was observed in 87.7% of cases and was significantly correlated with metastasis (p = 0.033) and clinical stage (p = 0.016). Immunoexpression of galectin-3 was observed in 87.7% of cases and was correlated with the presence of metastasis (p = 0.033) and histological grade of malignancy (p = 0.031). Galectin-4 showed no significant correlation with any of the parameters studied. Expression of galectin-7 was observed in 73.8% of cases and was significantly correlated with the histological grade of malignancy (p = 0.005). In conclusion, the intense immunoexpression of galectins-1, -3, and -7 suggests the participation of these proteins in oral carcinogenesis and their use as markers of biological behavior and tumor progression in squamous cell carcinoma of the tongue.     

High expression of integrin-linked kinase predicts aggressiveness and poor prognosis in patients with gastric cancer

Integrin-linked kinase (ILK), an intracellular serine/threonine protein kinase, has been reported to be highly expressed in many human malignancies, including gastric cancer. However, the prognostic significance of ILK expression in gastric cancer remains to be elucidated. In the present study, ILK expression in 95 gastric tumor tissues and 30 adjacent non-cancerous gastric mucosa was evaluated by immunohistochemistry and correlated with clinicopathological characteristics and patients’ outcome. The results showed that high ILK expression was observed in 47.4% (45/95) of gastric cancer tissues, but only in 20.0% (6/30) of adjacent gastric mucosa. Clinicopathological analysis indicated that high ILK expression was significantly associated with poor tumor differentiation (P = 0.024), advanced TNM stage (P = 0.006), tumor invasion (P = 0.001), and lymph node metastasis (P = 0.014). Kaplan–Meier survival curves demonstrated that patients with high ILK expression had substantially shorter overall survival that those with low ILK expression (P = 0.043, log-rank test). Furthermore, Cox multivariate regression analysis identified ILK expression as an independent prognostic factor for overall survival of gastric cancer patients (hazard ratio, 1.95; 95% confidence interval, 1.02–3.13; P = 0.026). In conclusion, our data suggest that ILK may contribute to the malignant progression of gastric cancer and serve as a novel prognostic indicator for gastric cancer patients.