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PubMed1984

Estrogen receptors and long-term prognosis in breast cancer.

The long-term prognosis in 233 primary breast cancer patients, most of whom had received ovarian irradiation, has been related to the estrogen-receptor status of the primary tumors. The median observation time was 9 years. The receptor status did influence disease-free interval and survival only in patients having metastases in axillary nodes. Thus, in the postmenopausal patients with axillary metastases, the disease-free interval and survival time were longer in receptor-positive than in receptor-negative patients during the first few years of observation. However, this difference disappeared in the course of the subsequent years. In the premenopausal women with axillary metastases the receptor status did not influence the short-term prognosis, and, unexpectedly, seemed to affect adversely the long-term prognosis. It is concluded that the long-term prognosis is no better in breast cancer patients having estrogen receptors in their primary tumors than in those with receptor-negative tumors.

Aged↗
PubMed1986

Prognosis and treatment after relapse of acute lymphoblastic leukemia and non-Hodgkin's lymphoma: 1985. A report from the Childrens Cancer Study Group.

Acute lymphoblastic leukemia and non-Hodgkin's lymphoma constitute 42% to 45% of the cancers in infants, children, and adolescents: In 1985, an estimated 2025 children were newly diagnosed with these two cancers and 900 (43%) of the pediatric cancer deaths in the United States have been projected to be due to these diseases. The single most important obstacle to preventing these deaths is relapse, and prevention of relapse or salvage of the patient who has had a relapse continues to be a major therapeutic challenge. The most important initial step in the treatment of the child whose disease has relapsed is to determine, to the extent possible, the prognosis. In a child with non-Hodgkin's lymphoma, a relapse confers an extremely poor prognosis, regardless of site of relapse, tumor histology, or other original prognostic factors, prior therapy, or time to relapse. In the child with acute lymphoblastic leukemia in relapse, the prognosis depends on multiple factors. The primary therapy is chemotherapy or chemoradiotherapy with marrow grafting. Other options exist, including no therapy, or investigational therapy. The therapy selected should be predicated on the prognosis. In the child with an isolated central nervous system (CNS) relapse off therapy, minimum therapy should be administered, particularly if the relapse occurred without prior cranial irradiation. In the child whose relapse is more than 6 months off therapy, conventional therapy should be considered. Also, a patient with an isolated CNS relapse on therapy after prior cranial irradiation should be given moderate therapy. Bone marrow transplantation or high-dose chemoradiotherapy with autologous marrow rescue should be reserved in children with a second or subsequent extramedullary relapse, and possibly for those with a first isolated overt testicular relapse on therapy.

Bone Marrow Diseases↗
PubMed1989

ras oncogene expression and prognosis of invasive squamous cell carcinomas of the uterine cervix.

By using anti-ras p21 mouse monoclonal antibody rp35, the authors studied the reactivity of 170 squamous cell carcinomas of the uterine cervix of different histologic types. The overexpression of p21 was noted in 57.1% of keratinizing type (K type) and 54.2% of large cell nonkeratinizing type (LNK type), but only 38.7% of small cell type (S type). Upon statistical analysis of the correlations between p21 overexpression and patient prognosis with the Kaplan-Meier method and generalized Wilcoxon text, the p21-positive K and LNK types showed poorer prognosis, whereas the positive S type showed better prognosis in comparison with the negative cases. These findings suggest that the expression of ras p21 is one of the parameters related with prognosis of cervical cancers, but the mode of the correlation is dependent on their histologic types.

Antibodies, Monoclonal↗
PubMed1993

Sequential trials of cisplatin, vinblastine, and bleomycin and etoposide and cisplatin in disseminated nonseminomatous germ cell tumors of the testis with a good prognosis at a single institution.

BACKGROUND: With the introduction of cisplatin-based chemotherapy, approximately 80% of patients with disseminated nonseminomatous germ cell tumors (NSGCT) of the testis can be cured. These treatments have been associated with considerable toxic effects. Numerous trials have been performed with the challenge of minimizing toxic effects without jeopardizing prognosis in a subgroup of these patients with a good prognosis. METHODS: A retrospective study comparing the efficacy and toxic effects of etoposide and cisplatin (EP) and cisplatin, vinblastine, and bleomycin (PVB) was done in two consecutive groups of patients who had comparable characteristics and disseminated NSGCT of the testis with a good prognosis. RESULTS: Twenty of 22 (91%) patients receiving EP and 19 of 19 (100%) receiving PVB achieved a complete response with or without adjunctive surgery. At surgery, similar proportions of patients in both groups were found to have mature teratoma or fibrosis and necrosis. With a median follow-up of 111 months (PVB-treated group) and 43 months (EP-treated group), the actuarial overall survival was similar in both groups. One patient treated with PVB and five patients receiving EP had relapses. The recurrence-free survival was almost significantly higher with PVB than with EP (P = 0.054). Only patients in the PVB-treated group had pulmonary (5.5%) and cutaneous (16%) toxic effects. No differences regarding hematologic, neurologic, and renal toxic effects were found. CONCLUSIONS: The omission of bleomycin in first-line therapy for disseminated NSGCT with a good prognosis should be adopted with caution because it seems to affect the therapeutic outcome, with more patients having relapses.

Adolescent↗
PubMed1993

Primary cutaneous CD30-positive large cell lymphoma: definition of a new type of cutaneous lymphoma with a favorable prognosis. A European Multicenter Study of 47 patients.

BACKGROUND: CD30 (Ki-1)-positive anaplastic large cell lymphoma (LCL) has been described as a morphologically distinct group of LCL that generally are associated with a poor prognosis. Recent studies indicate that these lymphomas, when confined to the skin, have a favorable prognosis. However, there is no consensus regarding the definition of these primary cutaneous CD30-positive LCL. Reported patients have been selected variously on the basis of morphologic (anaplastic cytology) or immunophenotypical (expression of CD30 antigen) criteria. METHODS: At two recent workshops aimed to achieve consensus on the definition and terminology of these lymphomas, the clinical, histologic, and immunophenotypical data of 47 patients with primary cutaneous CD30-positive LCL from five collaborating European centers were analyzed. RESULTS: Characteristic clinical features were presentation with solitary or localized skin lesions (42 of 47 patients), frequent cutaneous relapses (15 patients), and partial or complete spontaneous remission of skin lesions (11 patients). Twelve of 47 (25%) patients developed extracutaneous disease. The favorable prognosis of these lymphomas is indicated by the follow-up data that show that 36 of 47 patients are alive and in complete remission, only four disease-related deaths have occurred, and the overall median survival is 42 months (range, 2-130 months). There were no differences in clinical presentation, course, or prognosis between anaplastic and nonanaplastic CD30-positive LCL. CONCLUSION: The results of this study indicate that primary cutaneous CD30-positive LCL, regardless of their morphologic classification (anaplastic or nonanaplastic) can be considered as a distinct type of cutaneous T-cell lymphoma. Recognition of this type of cutaneous lymphoma is important because it may prevent patients from unnecessary aggressive treatment.

Adolescent↗
PubMed1994

S-phase fraction and nuclear size in long term prognosis of patients with breast cancer.

BACKGROUND: S-phase fraction (SPF) predicts the prognosis of patients with breast cancer independently of tumor size, axillary metastasis, estrogen receptor (ER) and progesterone receptor (PgR), and patient age. Whether SPF is best measured by DNA labeling index (SPF-LI) or by flow cytometry (SPF-Flow) and what is the relative efficacy of SPF versus histopathologic characteristics for prognosis have remained unanswered questions. METHODS: The authors studied 845 women with Stages I-II disease classification for years 1975-1990 with end results data, who were treated surgically with axillary lymph node dissection by an in vitro DNA labeling index protocol with tritiated thymidine or 5-bromo-2'-deoxyuridine and whose SPF was measured microscopically. Nuclear size was estimated with a calibrated optical grid as less than 11 microns, 11-14 microns, or greater than 14 microns. DNA flow cytometry was performed on fresh or paraffin embedded tissue; ER and PgR were performed by cytosol assay. Kaplan-Meier survival plots and multivariate analysis were used for comparisons. RESULTS: Tumor size, axillary lymph nodal status, SPF-LI, nuclear size, and ER all related strongly to breast cancer specific survival and relapse free survival. PgR was less effective. Lymph node status and tumor size predicted long term survival; differences for other variables largely disappeared by 10 years. By multivariate analysis, axillary lymph node status, tumor size, and ER were independently prognostic for disease specific, relapse free survival. A strong trend was found for nuclear size. PgR, DNA ploidy, and SPF did not contribute to prognosis independently. Nuclear size was the strongest independent predictor in patients with negative axillary lymph nodes. CONCLUSIONS: The number of positive axillary lymph nodes, tumor size, ER, and nuclear size were the strongest predictors of prognosis for patients with breast cancer. Only tumor size and lymph node status predicted the long term risk of metastasis.

Aged↗
PubMed1995

Prognosis of early esophageal cancer. Comparison between adeno- and squamous cell carcinoma.

BACKGROUND: The purpose of this study was to compare the prognosis of patients with T1 squamous cell carcinoma (SCC) with those with T1 adenocarcinoma of the esophagus and to explain prognostic differences by an analysis of clinicopathologic characteristics. METHODS: Seventy-seven patients with early esophageal cancer who underwent esophagectomy and lymphadenectomy from 1982 to 1993 were included in the study. Clinical and histopathologic characteristics, patterns of lymph node metastasis, results of surgery, and long term prognosis of 47 patients with SCC were compared with 30 patients with adenocarcinoma; a multivariate analysis of various prognostic factors was performed. RESULTS: The groups with adenocarcinoma and SCC were comparable regarding age, postoperative 90-day mortality (6.6% vs. 8.5%), infiltration of submucosa (74.5% vs. 80%), and rate of lymph node metastasis (17% vs. 16.6%). Cancer limited to the mucosa was not associated with lymph node metastasis in either group, whereas submucosal spread showed lymph node involvement in 21% of patients with adenocarcinoma and 26% of those with SCC. The 5-year survival rate of patients with complete tumor removal was superior for those with adenocarcinoma (82.5%) compared with those with SCC (59.2%) (P < 0.03). Multivariate analysis indicated that the histopathologic type (adenocarcinoma vs. SCC) was the only independent prognostic factor. The unfavorable prognosis of patients with T1 SCC was due to a higher recurrence rate and the more frequent development of second primary tumors (21% vs. 0%). CONCLUSIONS: The prognosis of patients with early esophageal cancer depends on the histologic tumor type. Patients with T1 SCC should be examined for another primary cancer before surgery and during follow-up.

Adenocarcinoma↗
PubMed1995

Clinicopathologic features and prognosis of resected hepatocellular carcinomas of varied sizes with special reference to proliferating cell nuclear antigen.

BACKGROUND: Proliferating cell nuclear antigen (PCNA) is an intranuclear protein that is linked closely to the cell cycle. An immunohistochemical study was performed on the expression of PCNA in various sized hepatocellular carcinomas (HCCs) to determine the relation between the proliferative activity of cancer cells and prognosis. METHODS: One hundred forty-one neoplasms resected from 141 patients who underwent hepatic surgery for HCC at Kyushu University hospital from April, 1991, to July, 1993, were studied immunohistochemically using monoclonal antibody for PCNA (PC10), and analyzed for a possible correlation between PCNA labeling index (PCNA-LI) and the prognosis of patients with HCC. RESULTS: Proliferating cell nuclear antigen reactive cancer cells were observed throughout the HCC. The PCNA-LI ranged from 1.2%-91.6%, with a mean of 37.7%. The high PCNA-LI (> 37.7) group showed a significantly higher incidence of tumor thrombus in the portal vein, higher Edmondson's Grade, and a higher recurrence rate than the low PCNA-LI (< 37.7) group. Hepatocellular Carcinomas were divided into three groups according to tumor size. Based on the clinicopathologic findings, in small (< 30 mm) HCCs, the high PCNA-LI (> 29.0) group showed a significant higher Edmondson's grade and a higher recurrence rate than the low PCNA-LI (< 29.0) group. In medium (30-60 mm) HCCs, the high PCNA-LI (> 36.1) group showed a significantly higher recurrence rate than the low PCNA-LI (< 36.1) group, although there was no difference in the pathologic findings between the high (> 59.4) and low (< 59.4) PCNA-LI groups. CONCLUSIONS: Proliferating cell nuclear antigen labeling index is closely related to cell differentiation and the prognosis of HCC. Furthermore, PCNA-LI was found to be useful in predicting the intrahepatic spread and prognosis of small (< 30 mm) and medium (30-60 mm) but not large (> 60 mm) HCCs.

Antigens, Neoplasm↗
PubMed1975

Prognosis after severe head injury.

Prognosis depends on establishing a relationship between the patient's state in the early stages and the ultimate outcome. Both the severity of the initial damage (including early complications) and the degree of recovery need to be defined, but practical and statistical considerations impose a limit on the number of variables which can be manipulated. Variables chosen should be those likely to be relevant, and pilot studies are more reliable than intuition in indicating which items should be included. Data chosen should be of a kind likely to be readily available for most patients and should not therefore depend on complex laboratory investigation. The most reliable indicant of initial severity appears to be the depth and duration of coma or altered consciousness, and a scale has been devised for measuring these. Measures of outcome should include separate assessment of mental and physical disability as well as the overall social consequence of the brain damage. Prognosis should be expressed as the probability (mathematically expressed) that a patient will reach certain defined outcome categories, five of which are recognized in the present study. Predictions should begin only after initial resuscitative measures are complete (say six hours after ictus); they need not be limited to the early stages but can include estimates of the degree of further improvement expected in the light of progress in the early weeks after injuries. New methods of management cannot be critically assessed unless factors influencing prognosis are reliably identified and can be matched in comparative patient groups. An estimate of prognosis is also required for the selection of patients for intensive treatment, both in the acute and in the rehabilitation stage. Without such data there is a tendency to deploy an unduly high proportion of scarce resources on patients who have little prospect of recovery; this may deny the best chance of recovery to patients with severe, but less overwhelming, brain damage.

Adult↗
PubMed2002

Association of proline-directed protein kinase FA with tumorigenesis, invasion, and poor prognosis of human colon carcinoma.

BACKGROUND: Initial studies revealed that the multisubstrate proline-directed protein kinase F(A) (PDPK F(A)) is overexpressed in various types of human carcinomas relative to normal controls. Suppression of overexpressed PDPK F(A) inhibits the growth of cancer cells, suggesting a role of this PDPK in human malignancy. In this study, we combine immunohistologic, molecular, cellular, animal, and clinicopathologic studies to demonstrate an essential and critical role of PDPK F(A) in progression and poor prognosis of human colon carcinoma. METHODS: The stable antisense clones of human colon carcinoma cells with specific suppression of PDPK F(A) were established for tumorigenesis and invasion studies. In immunohistologic and clinicopathologic studies, the expression and localization of PDPK F(A) were analyzed by immunohistochemical staining of the specimens obtained from human colon carcinoma patients with Dukes Stage B/C. RESULTS: Initial molecular and cellular studies revealed that the antisense clone of colon carcinoma cells (COLO-205) with specific suppression of PDPK F(A) dramatically lost capabilities of adhesion, chemotaxis, and invasion when compared with the parental or control-transfected colon carcinoma cells. This is the first indication of an association of overexpressed PDPK F(A) with colon carcinoma progression. In agreement with this notion, the in vivo study also revealed that the mice injected with the antisense clone with low-level PDPK F(A) only developed very small tumors (< 0.5 cm(3)) even after a 6-week observation. This is in contrast to the parental or control-transfected cells that developed large tumors (> 5 cm(3)) under identical conditions. Pathologic evaluation revealed invasion to the muscle layer in all tumors formed by the parental cells. In contrast, there was no sign of invasion in mice injected with the antisense clone, confirming an essential role of PDPK F(A) in colon carcinoma progression. Clinicopathologic study also revealed that PDPK F(A) is preferentially overexpressed in the invasive area of colon carcinomatous tissues and overexpression of PDPK F(A) is statistically and closely correlated with venous/lymphatic infiltration, lymph node metastasis, and poor prognosis of colon carcinoma patients with Dukes Stage B/C. CONCLUSIONS: The results demonstrate an essential and critical role of overexpressed PDPK F(A) in progression and poor prognosis of colon carcinoma patients. Suppression of overexpressed PDPK F(A) may provide a new powerful adjuvant approach to prevent human colon carcinoma progression and poor prognosis after surgery and chemotherapy.

Adult↗
PubMed2005

Akt phosphorylation is a risk factor for early disease recurrence and poor prognosis in hepatocellular carcinoma.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) who showed early massive disease recurrence due to hematogenous intrahepatic metastasis after curative resection had a poor prognosis. The authors previously reported that Akt phosphorylation was correlated with hematogenous intrahepatic metastasis, using HCC cell lines. METHODS: The authors analyzed clinicopathologic features and the status of selected biologic markers, including phosphorylated Akt, to identify risk factors for early disease recurrence and poor prognosis in HCC. In the current series, 49 postoperative patients developed intrahepatic disease recurrence within 6 months (Group 1) and 86 patients remained disease recurrence free > 3 years after resection (Group 2). Group 1 was further divided into 2 subgroups: 19 patients who died of disease recurrence within a year after resection (Group 1A) and 27 patients who survived > 1 year (Group 1B). RESULTS: Using univariate analysis, the risk factors for early disease recurrence were tumor size, macroscopic classification, tumor differentiation, microscopic capsule infiltration, microscopic portal vein (MPV) invasion, microscopic intrahepatic metastasis (MIM), and positive immunostaining for phosphorylated Akt, Ki-67, and p53 (P < 0.05). The risk factors for poor prognosis were the number of intrahepatic metastases, tumor differentiation, and positive immunostaining for phosphorylated Akt and Ki-67 (P < 0.05). Multivariate analysis revealed that the risk factors for early disease recurrence were MPV invasion, MIM, and positive immunostaining for phosphorylated Akt, and that the risk factors for poor prognosis were positive immunostaining for phosphorylated Akt and Ki-67 (P < 0.05). CONCLUSIONS: The current clinical study showed the critical involvement of Akt phosphorylation in the aggressiveness of HCC. The potential benefits of surgery should be assessed carefully in patients with any of these risk factors.

Aged↗
PubMed2005

Loss of function of p16 gene and prognosis of pulmonary adenocarcinoma.

BACKGROUND: Stepwise progression of peripheral-type lung adenocarcinoma was characterized morphologically and was related to prognosis. Expression of the tumor suppressor gene p16 in pulmonary adenocarcinoma decreased, mainly as a result of aberrant methylation of the CpG islands of the promoter region. METHODS: Aberrant methylation status of the p16 promoter region, the expression of its product, and loss of heterozygosity (LOH) on 9p21 were examined in surgically resected lung specimens from 57 patients (28 males and 29 females) with peripheral-type lung adenocarcinoma measuring </= 2 cm in diameter. RESULTS: Aberrant methylation of the p16 promoter region, negative p16 protein expression, and LOH of the 9p21 region were detected in 40.4%, 50.9%, and 40.4% of tumor samples, respectively. The alterations of the p16 gene were associated with poor prognosis, and in particular the prognosis of patients with aberrant p16 methylation was significantly worse than that of patients without aberrant methylation. These alterations also were associated with morphologic classification into bronchioloalveolar carcinoma (BAC) and non-BAC adenocarcinoma. Both aberrant methylation and LOH of 9p21 were associated with negative protein expression, but the former was correlated more closely with loss of function than was the latter. Cases with both alterations were completely negative for expression of the p16 gene product. CONCLUSIONS: Aberrant methylation of the promoter region of the p16 gene and loss of expression of its product were in accord with the multistep progression of peripheral-type lung adenocarcinoma, and these alterations were associated closely with poor prognosis of the disease.

Adenocarcinoma↗
PubMed1975

Initial features and prognosis in 363 children with acute lymphocytic leukemia.

The relationship of a variety of initial features and the outcome of therapy was analyzed for 363 children with acute lymphocytic leukemia (ALL). All had entered "total therapy" studies between 1962 and 1971. The standard for comparing outcome of therapy was whether patients with a given feature attained or exceeded the median duration of complete remission, hematologic remission or survival for the group. The results showed that, in general, the more massive or extensive the disease at diagnosis, the poorer the outcome. Factors associated with a significantly poorer prognosis included: initial leukocyte count above 100,000/mm; spleen enlargement greater than 5 cm; mediastinal involvement and early CNS involvement. Children over 10 years old at diagnosis and Negro children also had a poor prognosis. From another viewpoint features were examined for patients who attained at least 3 years of continuous complete remission. This confirmed some earlier findings and, in addition, showed that children under 2 years of age at diagnosis or with hepatomegaly over 5 cm were less likely to attain this goal. With the exception of early CNS involvement, however, patients with excellent responses to therapy were found with each factor of poor prognosis. Two major factors were not analyzed because their relationship to prognosis is generally accepted: therapeutic differences and acute nonlymphocytic leukemia.

Age Factors↗
PubMed1986

Malignancy index based on flow cytometry and histology for renal cell carcinomas and its correlation to prognosis.

Fifty-five human renal cell carcinomas, removed by nephrectomy, were classified using flow cytometry and histology. The parameters obtained by flow cytometry were DNA index, fractions of cells in the phases, and fractions of tumor cells versus normal cells. From histology, the routine classification of tumor structure and morphology were obtained, and a nuclear grading according to Arner et al. (Acta Chir Scand [Suppl] 346:1-12, 1965) was determined. All parameters including tumor stage according to Robson et al. (J Urol 101:297-301, 1969) were subjected to discriminant analysis in order to define a malignancy index. The patients were divided into two groups with good and poor prognosis (low and high risk). Those patients who were free of multiple metastases in 2 years and more after nephrectomy were assigned to the group "good prognosis"; those who developed multiple metastases for 2 years represented the "poor prognosis" group. The malignancy index determined by discriminant analysis yielded 91% correct predictions of prognosis.

Carcinoma, Renal Cell↗
PubMed2003

Infiltrating immune cells, but not tumour cells, express FasL in non-small cell lung cancer: No association with prognosis identified in 3-year follow-up.

Non-small cell lung cancer (NSCLC) remains a difficult disease to treat and independent prognostic markers other than tumour stage and histology have not emerged. The immune cell content of solid tumours has been associated with tumour regression and at times, tumour progression. The involvement of immune cells in prognosis of NSCLC is poorly described. Poor immune responses within solid tumours have been linked with tumour production of immunosuppressive cytokines. Tumour expression of FasL is thought to disarm responses through the transduction of a death signal in Fas-expressing T cells. The existence of the 'tumour counterattack' in vivo has been questioned. We undertook to measure T cell and macrophage infiltration of the tumour bed in NSCLC and report the association between immune cell content and prognosis in a limited, 3-year analysis of survival (n = 113). In addition we investigated FasL expression (n = 45). T cells and macrophages were found to frequently infiltrate lung tumours, albeit in small numbers. Generally there were more T cells infiltrating than macrophages. T cell and macrophage numbers were not associated with prognosis. Lung tumours were found not to express FasL, although occasional immune cells surrounding tumour cells were strongly positive. FasL expression was not associated with prognosis in this series. Thus, immune cells infiltrating NSCLC are not capable of suppressing tumour growth, nor are they associated with tumour progression. We report that lung tumours do not express the FasL, and that although some immune cells are FasL positive, this is not a reflection of general immune cell activation.

Adenocarcinoma↗
PubMed2004

Childbirth and breast cancer prognosis.

Although certain risk factors for breast cancer incidence may also effect survival, findings have been inconsistent and the long-term role of childbirth is unknown. We studied the influence of number and timing of births on breast cancer prognosis prospectively. From 1958 to 1997, altogether 32,003 women, born 1932 or later, were notified to the Swedish Cancer Registry due to a primary invasive breast cancer. We obtained information on dates of all childbirths and achieved complete follow-up through 1997 by means of linkage to other nation-wide databases. Proportional hazards analyses were used to compute crude and multivariate hazard ratios (HR) with 95% confidence intervals (CI) of dying from breast cancer. We found a successively worse prognosis for women with a shorter delay between their last birth and breast cancer diagnosis (p for trend <0.0001). Compared to women with their last birth more than 10 years before diagnosis, the multivariate HR of breast cancer death was 1.39 (95% CI 1.17-1.67) for those with breast cancer diagnosis in the 3rd year after last birth and 1.72 (CI 95% 1.42-2.09) for those with diagnosis within 1 year after last birth. This adverse effect on prognosis of childbirth persisted beyond 10 years among women with a first birth before the age of 20 years. A pregnancy has marked adverse effects on the prognosis of a breast cancer diagnosed within 10 years after delivery. These findings suggest that pregnancy influences tumor biology.

Adult↗
PubMed2004

Reduced expression of class II histone deacetylase genes is associated with poor prognosis in lung cancer patients.

HDAC genes are thought to be involved in gene expression through the regulation of chromatin structure, alterations of which may cause abnormal gene silencing in cancers. To clarify the possible role of HDAC genes during tumor development and progression, we studied their expression and influence on clinical features. Expression levels of HDAC class I and class II genes in cancer tissues resected from 72 patients with NSCLC were measured with real-time RT-PCR. Their association with clinicopathologic features was statistically investigated. Reduced expression of each class II HDAC gene was significantly associated with poor prognosis and an independent predictor of poor prognosis. Of all the genes, HDAC10 was the strongest predictor of poor prognosis. Hierarchical clustering analysis showed that lung cancer tissues could be divided into 3 groups based on the expression level of class I and class II HDAC genes. The group with reduced expression of class II HDACs showed poor prognosis. These results suggest that class II HDACs may repress critical genes and that low expression of these genes may play a role in lung cancer progression. Results of clustering analyses imply that class II HDAC genes may be regulated by a similar mechanism and deregulated during cancer development.

Adenocarcinoma↗
PubMed1992

Levels of expression of breast epithelial mucin detected by monoclonal antibody BrE-3 in breast-cancer prognosis.

Taking into consideration the relationship of breast neoplasia with recent knowledge obtained on the molecular structure and biosynthesis of the breast epithelial mucin, an epitope on this molecule detected by monoclonal antibody (MAb) BrE-3 was chosen as a marker to study the correlation of expression of the mucin and prognosis in infiltrating ductal carcinomas of the breast. Strong statistical validation was obtained in the use of BrE-3 in immunohistochemical procedures where scores for the expression of the mucin on paraffin-embedded sections of the primary breast tumors were studied. Four different immunohistochemical variables measuring levels of expression (intensity or prevalence) in cytoplasm or membrane were obtained for each of 227 patients' breast tumors and subjected to Kaplan-Meier univariate and Cox proportional-hazards multi-variate analysis. Additionally, traditional prognostic variables for breast-cancer prognosis (grade of differentiation, age, tumor size, axillary-lymph-node involvement and estrogen receptors) were subjected to identical analyses. In uni-variate analysis, low cytoplasmic intensity, high membrane prevalence, and high membrane intensity of mucin expression were each found to be significantly associated with good prognosis in relation to both survival or relapse time. In multi-variate analysis, all 4 immunohistochemical parameters were significantly associated with both survival and relapse time in these patients. Among the traditional variables, 3 (axillary-node involvement, grade of differentiation and tumor size) were also found to be statistically significant at the uni-variate and multi-variate level. A multi-variate analysis of the combined immunohistochemical and traditional variables identified the 4 immunohistochemical parameters, tumor size and axillary-node involvement as having the highest level of association with either survival or relapse time. These variables were then combined and served to define a prognostic model [ILCPS(Comb)], which was found to have the capacity to separate the patient population studied into 4 prognostic groups in terms of survival and 3 groups in terms of relapse. As expected, the ILCPS(Comb) was shown to have a higher level of prognostic association with both survival and relapse than the individual variables themselves, the traditional variables together or the immunohistochemical variables together. Our approach develops a theoretical framework and a statistical model, employing levels of expression of the breast epithelial mucin and 3 traditional variables, which identifies, in terms of prognosis, distinct sub-populations of patients with infiltrating breast carcinoma with defined risk functions.

Adolescent↗