Prognostic significance of human tissue kallikrein-related peptidases 11 and 15 in gastric cancer.

Human tissue kallikrein-related peptidases (KLK) are a group of 15 serine proteases which have been investigated as potential cancer biomarkers. This study determined the prognostic significance of KLK 11 and 15 expression levels in gastric carcinoma specimens. Expression of KLK11 and KLK15 was assessed by immunohistochemistry staining on a tissue microarray constructed from 113 gastrectomy specimens from patients with gastric carcinoma. To minimize inter-observer variability, expression levels were quantified using an automated algorithm. Epithelial and stromal staining were assessed separately. Both KLK11 and KLK15 were expressed in gastric carcinoma. There was no significant correlation between either KLK11 or KLK15 expression and the presence of lymph node metastases or Lauren classification (intestinal vs. diffuse). Higher levels of KLK11 expression in gastric carcinoma were associated with significantly worse overall survival (p = 0.008), and a multivariate analysis showed that it had prognostic value independent of tumor stage and differentiation (p = 0.004). Variations in KLK15 expression were not significantly associated with prognosis. KLK11 shows promise as a potential independent prognostic marker for gastric carcinoma.

Prognostic significance of human tissue kallikrein-related peptidases 6 and 10 in gastric cancer.

The prognosis of patients following surgery for gastric cancer is often poor and is estimated using traditional clinicopathological parameters, which can be inaccurate predictors of future survival. Kallikreins are a group of serine proteases, which are differentially expressed in many human tumors and are being investigated as potential cancer biomarkers. This study assessed the prognostic utility of human tissue kallikrein-like peptidases 6 and 10 (KLK6 and KLK10) and correlated their expression with histopathological and clinical parameters in gastric cancer. We constructed a gastric tumor tissue microarray from 113 gastrectomy specimens and quantified KLK6 and KLK10 expression using immunohistochemistry. To overcome the problem of inter-observer variability and subjectivity in immunohistochemistry interpretation, a whole-slide scanned image of the tissue microarray was analyzed using an automated algorithm to quantify staining intensity. KLK6 expression was positively correlated with nodal involvement (p=0.002) and was predictive of advanced-stage disease (p<0.05). Kaplan-Meier survival curves revealed that tumors expressing high levels of KLK6 were significantly associated with significantly lower overall survival (p=0.04). KLK10 overexpression was also a predictor of advanced-stage disease (p<0.01), but was not significantly correlated with lymph node involvement or survival period. Our results show the potential ability of KLK6 as a prognostic marker for gastric cancer.

Evaluation of human tissue kallikrein-related peptidases 6 and 10 expression in early gastroesophageal adenocarcinoma.

Kallikreins are a family of serine proteases that are linked to malignancy of different body organs with potential clinical utility as tumor markers. In this study, we investigated kallikrein-related peptidase 6 (KLK6) and KLK10 expression in early gastroesophageal junction adenocarcinoma and Barrett esophagus (BE) with and without dysplasia. Immunohistochemistry revealed significantly increased KLK6 expression in early invasive cancer compared with dysplastic (P = .009) and nondysplastic BE (P = .0002). There was a stepwise expression increase from metaplasia to dysplasia and invasive tumors. Significantly higher KLK10 was seen in dysplastic lesions compared with metaplasia but not between dysplastic lesions and invasive cancers. KLK6 staining intensity was increased at the invasive front (P = .006), suggesting its role in tumor invasiveness. Neither KLK6 nor KLK10 was significantly associated with other prognostic markers, including depth of invasion, indicating their potential as independent biomarkers. Our results should be interpreted with caution due to limited sample size. There was a significant correlation between KLK6 and KLK10 expression both at the invasive front and within the main tumor, indicating a collaborative effect. We then compared KLK6 and KLK10 messenger RNA expression between metaplastic and cancerous tissues in an independent data set of esophageal carcinoma from The Cancer Genome Atlas. KLK6 and KLK10 may be useful markers and potential therapeutic targets in gastroesophageal junction tumors.

Cancer survival as a function of age at diagnosis: a study of the Surveillance, Epidemiology and End Results database.

BACKGROUND: Recent research suggested that cancer survival has improved in recent cohorts. Improvement in cancer survival is considered a valid indicator of the quality of care introduced to the patients. The aim of this study is to investigate the changes in the survival profile over age for patients with the most incident cancers. METHODS: Survival data of 3.94 million patients diagnosed with 23 primary-site cancers within the periods of 1979-1983, 1989-1993, and 1999-2003 were adopted from the Surveillance, Epidemiology and End Results database. Gender and cause-specific survival probabilities were estimated at one, three, and five years after diagnosis using the Kaplan-Meier survival estimate. Survival was presented for each of the studied cancers, cohorts, and sexes in the form of line graphs as a function of age at diagnosis. Error bars demonstrated the probability of error at 95% confidence level. RESULTS: The graphs demonstrated that cancer survival was improved over the successive cohorts for most cancers, with several exceptions such as brain and lung cancers. The relation between survival and the age at diagnosis was generally described in the form of a gradual decline phase and a rapid fall-off phase at 70-80 years of age, with few exceptions as in leukemia and Hodgkin lymphoma. Patients who survived for three years were more likely to live for five years after diagnosis, but this prediction could not be extrapolated to the one-year survivors. CONCLUSION: Further studies on tumor-specific characteristics and treatment modalities of these patients are suggested for clarification of the possible causes of variations in patient's survival profile over age.