Metastatic lymph node ratio as a prognostic factor in gastric cancer.

BACKGROUND: There is an association between the number of resected lymph node and the number of metastatic lymph nodes in gastric cancer, suggesting that pN category could be influenced by the extension of the lymphadenectomy. This study evaluates this association and proposes a comprehensive use of the ratio as prognostic factor. METHOD: Review of 183 consecutive patients with gastric adenocarcinoma. The association between the number of resected lymph nodes and the number of metastatic lymph nodes was analysed and evaluated with other prognostic factors. RESULTS: The number of lymph node metastases increased with the number of resected lymph nodes. The lymph node ratio was a better prognostic factor than the number of metastatic lymph nodes. CONCLUSIONS: The metastatic lymph node ratio seems to be a good prognostic factor, but needs further evaluation.     

E-cadherin and c-met expression as a prognostic factor in gastric cancer

E-cadherin has an important role in the cell-cell adhesion and is known as an invasion suppressor gene. The c-met, which is a receptor of hepatocyte growth factor receptor, is involved in the proliferative and motile activity in cancer cells. The invasive and metastatic capacities of gastric cancer were studied from the immunohistochemically examined expression of MET and E-cadherin. Among 127 primary gastric cancers, 47 (34%) tumors were found to have preserved E-cadherin expression and the other 84 tumors showed reduced E-cadherin expression. MET expression was found in 55 (43%) tumors. A strong correlation was found between reduced E-cadherin expression and a larger tumor, positive serosal invasion, lymph node metastases or poor prognosis. Tumors with MET expression have the tendencies to invade deeply, to metastasize in more remote lymph nodes or peritoneum and to run a poor prognosis. MET over-expression and reduced E-cadherin expression were strongly associated with lymph node metastasis, peritoneal dissemination and poor prognosis. This group of patients with simultaneously abnormal expressions of these genes had a sixfold relative risk of death, as compared with patients with tumors showing MET negative or preserved E-cadherin expression. These results indicate that immunohistochemical combined analyses of MET and E-cadherin expression may be a powerful tool for the evaluation of invasive capacity and the prognosis of gastric cancer patients.     

Peritoneal lavage cytology findings as prognostic factor for gastric cancer.

The validity of lavage cytology for accurate gastric cancer staging is demonstrated in this study. Between 1988 and 1996, 29 cases (8. 4%) were revealed as positive among 347 patients with resectable gastric cancer in whom peritoneal lavage cytology was performed. The survival rate of cytology-positive patients in each stage was found to be worse than that of all other patients in the same stage. The prognostic factors selected by the univariate analysis were enrolled for multivariate analysis using Cox's proportional hazards model with the backward stepwise procedure. As a result, although cytology finding was selected as an independent prognostic factor, macroscopic finding of dissemination was not selected. Our data indicate that positive cytology findings indicated a poor prognosis, and therefore the results of peritoneal lavage cytology should be included as a factor in gastric cancer staging.     

Matrix metalloproteinase-9 as a prognostic factor in gastric cancer: a meta-analysis

Background: Matrix metalloproteinase-9 (MMP-9) is associated with disruption of basement membranesof blood vessels and promotion of metastasis through the lymphatics. However, its prognostic value for survivalin patients with gastric cancer remains controversial. Method: We therefore conducted a meta-analysis of thepublished literature in order to clarify the impact of MMP-9. Clinical studies were selected for further analysisif they provided an independent assessment of MMP-9 in gastric cancer and reported analysis of survival dataaccording to MMP-9 expression. Results: A total of 11 studies, covering 1700 patients, were included for metaanalysis.A summary hazard ratio (HR) of all studies and sub-group hazard ratios were calculated. The combinedHR suggested that a positive MMP-9 expression had an impact on overall survival: 1.25 (95% confidence interval1.11-1.40) in all eligible studies; 1.13 (1.06-1.20) in 8 studies detecting MMP-9 by immunohistochemistry; 1.36(1.12-1.65) in 7 studies from Asia. Only one study for DFS showed a significant impact on disease free survival(HR 1.73, 95%CI 1.27-2.34). Conclusions: Our findings suggested that MMP-9 protein expression might be afactor for a poor prognosis in patients with gastric cancer. However, the association was rather weak, so that moreprospective studies should further explore the prognostic impact of MMP-9 mRNA and correlations betweenMMP-9 and clinicopathological characteristics.     

PGP9.5 as a prognostic factor in pancreatic cancer.

The expression of PGP9.5 was evaluated using immunohistochemistry in 69 resected ductal carcinomas of the pancreas and in normal pancreatic tissue. Overexpression did not seem to differ with histological type or pathological stage. A significant negative correlation was found between overexpression of PGP9.5 and postoperative survival. Multivariate analysis also suggested PGP9.5 along with tumor stage and extrapancreatic plexus invasion as strong predictors of the outcome. This study suggests that PGP9.5 expression may be used as a marker for predicting the outcome of resection-treated pancreatic cancer patients.     

Grading as a prognostic factor: review of 209 primary gastric cancer patients

Two hundred and nine cases of primary gastric cancer were treated surgically from January 1968 to December 1983 and analyzed retrospectively. All patients were followed up for a minimum of 5 years. There were 25 SI cases (12%), 22 SII (10.5%), 55 SIII (26.3%) and 107 SIV (51.2%). Tumor grade according to Broders classification showed 50 cases of G1 lesions (23.9%), 44 G2 (21.1%) and 115 G3 (55%). Patients with well differentiated G1 lesion, compared to G2-G3 patients, presented a greater incidence of T1-T2 tumors and decreased incidence of T4 tumors (p less than 0.05). The lymph node involvement rate significantly increased with variation of T (p less than 0.001) but not with tumor grade. Survival results correlated with tumor stage (p less than 0.01) but not with tumor grade or histological type.     

Aneuploidy as a prognostic factor in breast cancer

The predictive value of nuclear DNA content in mammary carcinoma is still under debate in spite of several reports indicating a relationship between DNA ploidy and prognosis. The impact of differences in methodology on the evaluation of DNA data is discussed, and a recent study demonstrating DNA ploidy as a statistically significant prognostic variable on a prospective material of breast cancer patients is presented.     

Age as a prognostic factor in breast cancer

The influence of age on survival was studied in an unselected series of 31,594 females with breast cancer reported to The Cancer Registry of Norway during 1955-1980. The prognosis was best in patients aged 35 to 49 years, and poorest in the older (greater than or equal to 75 years) and the younger patients (less than or equal to 34 years). These trends were present in all stages and periods of diagnosis. The poor outcome among the older patients may, in part, be related to less aggressive treatment, while differences in treatment procedures hardly explain the poor prognosis among the younger patients.     

Age as a prognostic factor in breast cancer

Long-term survival was evaluated in a total of 12,319 women with first breast cancer, comprising 94.9% of virtually all women with first breast cancers diagnosed in Sweden in 1959 through 1963. After correction for the expected mortality, it was found that age at diagnosis was an important predictor of the probability of escaping the risk of dying of breast cancer (relative survival), with a regular trend toward a more favorable course in younger women. This difference between the age groups is apparent as early as 5 years after diagnosis and increases throughout the period of observation. Thus the relative 20-year survival rates +/- 95% confidence limits were 51.3 +/- 3.8%, 41.2 +/- 3.4%, 34.2 +/- 3.8%, and 16.6 +/- 6.3% at ages 40 through 44, 50 through 54, 60 through 69, and 70 through 79 years, respectively. Patients younger than 40 years diverged from the general trend, with a survival rate of 44.1 +/- 4.6% at 20 years.     

Aneuploidy as a prognostic factor in breast cancer

The predictive value of nuclear DNA content in mammary carcinoma is still under debate in spite of several reports indicating a relationship between DNA ploidy and prognosis. The impact of differences in methodology on the evaluation of DNA data is discussed, and a recent study demonstrating DNA ploidy as a statistically significant prognostic variable on a prospective material of breast cancer patients is presented.     

Plasma bikunin as a favorable prognostic factor in ovarian cancer.

PURPOSE: Bikunin is a multifunctional glycoprotein, which mediates suppression of tumor cell invasion and metastasis. The measurement of bikunin levels in the tissue of patients with malignant diseases has been introduced as a new and simple diagnostic tool for the evaluation of prognosis. The high bikunin expression in ovarian cancer tissue would enable the use of soluble bikunin protein present in the circulation of ovarian cancer patients as a biomarker of disease. PATIENTS AND METHODS: We developed a double-antibody immunoassay for bikunin and detected its presence in normal human circulation. We quantified, by enzyme-linked immunosorbent assay and/or immunoblot assay bikunin in sera from 200 healthy women (controls), 200 patients with benign gynecologic diseases, and 327 patients with ovarian cancer before surgical removal of the tumor. RESULTS: When the values of bikunin corresponding to the median were used as the cutoff value (11.5 microg/mL), low plasma bikunin was strongly associated with late-stage, suboptimal debulking with large residual tumor (> 2 cm) and low response to chemotherapy. The median survival time of the patients with a high bikunin level was more than 60 months as compared with 26 months among those with low bikunin level (P = .002). This difference corresponded to a 2.2-fold increased risk of dying for the lower plasma bikunin patients (hazard ratio, 0.45; P = .023) and remained significant in multivariate analysis (hazard ratio, 0.63; P = .041). CONCLUSION: Preoperative plasma bikunin concentration is a strong and independent favorable prognostic marker for ovarian cancer.     

Proliferative activity as a prognostic factor in Borrmann type 4 gastric carcinoma.

Proliferative activities in 181 primary Borrmann type 4 gastric carcinomas were investigated using percentage labelling of proliferating cell nuclear antigen (PCNA) and an argyrophilic nucleolar organiser region (AgNOR) count. Tumours with a high proliferative activity often metastasised to lymph nodes (P < 0.01), and these patients had a lower survival rate (P < 0.05). A significant correlation was recognised between the PCNA labelling percentage and AgNOR count (r = 0.452, P < 0.001). Cox''s regression analysis showed that PCNA labelling percentage is an independent prognostic factor. These results indicate that estimating proliferative activity may be useful in predicting lymph node metastasis and patients'' prognosis in cases of Borrmann type 4 gastric carcinoma.     

Matrix metalloproteinase-2 is a consistent prognostic factor in gastric cancer

In a pioneer study, we showed 10 years ago that enhanced tissue levels of the matrix metalloproteinases (MMPs) MMP-2 and MMP-9 in gastric cancers, as determined by zymography, were related with worse overall survival of the patients. To corroborate these observations, we now assessed MMP-2 and MMP-9 with new techniques in an expanded group of gastric cancer patients (n = 81) and included for comparison MMP-7, MMP-8 and the tissue inhibitors of MMPs, TIMP-1 and -2. All MMPs and TIMP-1 were significantly increased in tumour tissue compared to normal gastric mucosa. Matrix metalloproteinase-7, -8 and -9, and the TIMPs showed some correlations with the clinicopathologic parameters TNM, WHO and Laurén classification, but their levels were not related with survival. Regardless of the determination method used, that is, enzyme-linked immunosorbent assay or bioactivity assay, an enhanced tumour MMP-2 level did not show a significant correlation with any of the clinicopathological parameters, but was confirmed to be an independent prognostic factor in gastric cancer.     

Tumor regression as a prognostic factor in breast cancer

Two hundred and fifty evaluable patients with breast cancer entered a protocol combining neoadjuvant and consolidation therapy by vinblastine (V), thiotepa (T), methotrexate (m) and 5-fluorouracil (f) (VTMF) with or without Adriamycin (A) (Doxorubicin; Adria Laboratories, Colombus, OH USA), and radiation therapy as exclusive locoregional treatment. Tamoxifen was given to 195 patients, 130 post menopausal and 65 pre-menopausal, and was omitted in 55 patients (31 postmenopausal and 24 pre-menopausal). There were 19 stage I, 86 IIa, 51 IIB, 36 IIIA and 58 IIIB. Primary chemotherapy induced tumor volume regression of more than 75% in 41% of the patients and complete clinical regression in 30% of the patients. The 5 years DFS rates were 100% for stage I, 82% for stage IIA, 61% for stage IIB, 46% for stage IIIA and 52% for stage IIIB patients. Among the 72 primary relapses there were 39 distant metastases, 6 locoregional and distant metastasis and 27 isolated locoregional metastases. The actuarial rate of locoregional recurrence is 13% for T2, 18% for T3, 19% for T4. At 5 years the rate of breast preservation was 94%. Cosmetic results are excellent or good for most patients. The 5 years overall survival (OS) were 95% for stage I, 94% for stage IA, 80% for stage IIB, 60% for stage IIIA and 58% for stage IIIB. In multivariate analysis tumor regression appears as an independent and significant factor. This parameter should be preserved in many patients with infiltrative breast cancer.     

Age as a prognostic factor in recurrent breast cancer

The effect of age as a prognostic factor in recurrent breast cancer was studied in 1,168 patients treated on Eastern Cooperative Oncology Group (ECOG) protocols. Survival was significantly shorter in patients less than 35 years of age (P = .03). This was true even when other good prognostic factors were present. Eighteen prognostic factors were analyzed, and the effect on survival in each of six age groups was studied. Patients with better performance status, less than three sites of metastases, and without visceral or nodal metastases had a better survival time. A Cox proportional hazards model of survival showed that younger age groups, irrespective of menopausal status, had shorter survival times. The predicted median survival times after the first recurrence were 491 days for patients less than 35 years of age, 590 days for patients 36 to 45 years of age, and 700 days for those greater than 45 years of age.     

Neutrophil-lymphocyte ratio as a prognostic factor in colorectal cancer

BACKGROUND AND OBJECTIVES: Simple methods to identify colorectal cancer patients at risk of recurrence are needed. This study aimed to determine if neutrophil-to-lymphocyte ratio (NLR) predicts survival in colorectal cancer patients. METHODS: Two-hundred thirty patients diagnosed with colorectal cancer over a two-year period were identified from a prospectively maintained colorectal cancer database. NLR was calculated from pre-operative full blood counts. In the case of patients who did not undergo surgery, the full blood count from their out-patient visit was used. Known prognostic factors were recorded. Overall and cancer-specific survival were calculated. RESULTS: Pre-operative NLR greater than 5 correlated with overall and cancer-specific survival in univariate analyses. NLR was not independent of Dukes stage. CONCLUSIONS: Pre-operative NLR may represent a simple method of identifying colorectal cancer patients with a poor prognosis pre-operatively.     

Thrombocytosis as a prognostic factor in inflammatory breast cancer

Purpose

Platelets are essential components of hemostasis and also play an important role in the tumor microenvironment. The purposes of our research were to examine the role of thrombocytosis in inflammatory breast cancer (IBC) and to know which cytokine drives thrombocytosis.

Methods

We reviewed the medical records of 3654 patients with stage I–III breast cancer treated between 1998 and 2013, including 230 patients (6%) with IBC. We used Chi-squared test or Fisher’s exact test to compare the variables between patients with and without thrombocytosis. Multivariate Cox regression models were used to determine the association of thrombocytosis with overall survival. We also examined baseline serum cytokine levels in 81 patients with primary IBC to determine the association of inflammatory cytokines with thrombocytosis.

Results

We found that thrombocytosis was the only variable that predicted prognosis. Fifty-five patients (1.5%) had thrombocytosis. Thrombocytosis was more prevalent in patients with IBC than in those with non-IBC (3.4% vs. 1.4%, p = 0.015). In patients with IBC, thrombocytosis was associated with worse overall survival [hazard ratio 2.38, 95% confidence interval (CI) 1.05–5.4, p = 0.0378]. Circulating levels of growth-regulated oncogene (GRO) (odds ratio 1.003, 95% CI 1.001–1.005, p = 0.0019) and transforming growth factor β (TGF-β) (odds ratio 1.3, 95% CI 1.128–1.499, p = 0.0003) were associated with thrombocytosis.

Conclusions

Thrombocytosis was more prevalent in patients with IBC than in those with non-IBC and it was associated with poor prognosis. GRO and TGF-β were associated with thrombocytosis in IBC.

     

Reticuloendothelial function as a prognostic factor in breast cancer

Reticuloendothelial function was investigated in breast cancer by the 131I-microaggregated albumin method using the parameters of phagocytic function (K value) and metabolic function (M value). Reticuloendothelial function of the patients with breast cancer was decreased compared with that of the controls, and it was related to the peripheral lymphocyte count. This finding indicates that reticuloendothelial function is one of the prognostic factors in breast cancer.