Methyl-p-hydroxyphenyllactate-esterase activity in breast cancer: a potentially new prognostic factor in short-term follow-up.

We assayed methyl-p-hydroxyphenyllactate esterase (MeHPLAase) activity in 48 cases of primary breast cancer. MeHPLAase activity did not show significant correlation with estrogen receptor and progesterone receptor levels. No significant relationship was found between enzymatic activity and tumor diameter, lymph node status, mitotic activity, degree of nuclear differentiation, and proportion of the S-phase fraction. During the follow-up period (median, 18.8 months; range, 6-69 months), recurrences were observed in 18 of 48 (37%) cases. The Weibull survival regression model using the enzymatic activity as a continuous covariate showed that levels of enzymatic activity were directly associated with the risk of recurrence (P = 0.02). Assuming the mean value of enzymatic activity as the cutoff value, we found a statistically significant relationship between high MeHPLAase activity and shorter recurrence-free survival. On multivariate analysis, MeHPLAase activity proved to be an independent factor for predicting a short period of recurrence-free survival.

Detection of synaptophysin-producing cells in human thymus by immunohistochemistry and nonradioactive in situ hybridization.

We investigated human thymic tissue by immunohistochemistry and in situ hybridization for the presence of synaptophysin-producing cells. Our results indicate that anti-synaptophysin antibody detected immunoreactive material in nerve fibers around vessels located in major thymic septa, in a relevant number of cortical epithelial cells, and in scattered epithelial cells in the medulla. The epithelial nature of synaptophysin-positive cells was documented by the co-expression of cytokeratins as revealed by double immunofluorescence. In situ hybridization studies revealed the presence of synaptophysin mRNA in cells mainly located in the cortex, the specific fluorescent signals being localized in the cell cytoplasm. Western blot analysis using an affinity-purified polyclonal antibody revealed an immunoreactive band of about 38 kD in the extracts from unfractionated thymic tissue and from epithelial cell-enriched fractions. No staining was observed in isolated thymocytes. The expression of synaptophysin in epithelial cells of the thymic cortex suggests that this protein may be involved in secretory activities related to T-cell maturation.

Long-lasting complete remission in plasma cell leukemia after aggressive chemotherapy and CD34-selected autologous peripheral blood progenitor cell transplant: molecular follow-up of minimal residual disease.

Plasma cell leukemia is a rare disease associated with very poor survival with standard treatment. We report a patient affected by plasma cell leukemia treated with aggressive chemotherapy and autologous CD34-selected PBPC who achieved a complete remission now lasting more than 2 years. Molecular studies confirmed the presence of minimal residual disease (MRD) despite the absence of disease activity. High-dose chemotherapy with stem cell rescue may be applied to selected patients considering the impact of the treatment on survival. The meaning of molecular MRD in this setting is unclear.

Immunohistochemical and in situ hybridization detection of growth-hormone-producing cells in human thymoma.

We have studied 25 thymomas by both immunohistochemistry and in situ hybridization for the presence of growth hormone (GH)-producing cells. Our results indicate that 1) GH-immunoreactive cells were present in 13 of 17 thymomas of cortical and predominantly cortical type but not in medullary (spindled) thymomas (n = 3) or low- to high-grade thymic carcinomas (n = 5), 2) GH-positive cells were mainly located at the periphery of the neoplastic lobules, at the periphery of the perivascular spaces and in the areas of medullary differentiation, 3) cells containing GH mRNA appeared at locations similar to those of GH-immunoreactive cells, and 4) GH-immunoreactive material was present only in the epithelial cell component as revealed by immunoelectron microscopy. In conclusion, this paper demonstrates the occurrence of GH-producing cells in noncarcinoid thymic tumors. The relevance of GH in thymoma cell biology requires additional investigations.

Quercetin inhibits p21-RAS expression in human colon cancer cell lines and in primary colorectal tumors.

Immunocytochemical studies have revealed that 10 microM quercetin reduced the steady state levels of p21-ras proteins in both colon cancer cell lines and primary colorectal tumors. These findings were confirmed by Western blot and flow cytometric analysis showing that the inhibition of p21-ras expression by quercetin was time- and concentration-dependent. Twenty-four-hour treatment with 10 microM quercetin reduced p21-ras levels to about 50% of control values. Quercetin was similarly effective in inhibiting the expression of K-, H-, and N-ras proteins. Moreover, the effect of quercetin on ras oncogene expression was not dependent on the cell cycle position of colon cancer cells and appeared to be specific and not merely a consequence of overall inhibition of protein synthesis. Northern blot analysis revealed that quercetin produced in colon cancer cells an early (30 min) reduction of the steady state levels of K-, H-, and N-ras mRNAs. This reduction was also present after 6 hr of flavonoid treatment. These effects of quercetin suggest a possible chemopreventive role for this compound in colorectal carcinogenesis.

Autologous graft-versus-host disease after CD34+-purified autologous peripheral blood progenitor cell transplantation.

Autologous graft-versus-host disease (GVHD) has been frequently reported after cyclosporine A (CsA) administration in the autologous setting. This complication is related to the disruption of self-tolerance mechanisms induced by CsA and may exert an antitumor effect. We report the spontaneous occurrence of autologous GVHD after CD34+-purified peripheral blood progenitor cell transplantation (PBPCT) in 5 out of 24 consecutive patients (20.8%). The syndrome was characterized by skin rash (5/5), pruritus (5/5), eosinophilia (5/5), and fever (2/5) occurring at a median of 37 days (range 22-60) after transplantation. Diagnosis was confirmed by skin biopsy in all patients. The syndrome was self-limiting, lasted a median of 25 days, and did not require treatment. The rate of autologous GVHD was high after CD34+-purified autologous PBPCT. In fact, no autologous GVHD was documented in an historical control of 100 consecutive patients submitted to unmanipulated PBPCT at the same institution. The manipulation of the graft by the purging procedure causes a profound T lymphocyte depletion, thus possibly perturbing the equilibrium between autoregulatory cells and autocytotoxic T cells. These observations add new interest to the antitumor efficacy of autologous GVHD and suggest new questions regarding the role of transplantation for autoimmune diseases.

Prognostic significance of methyl-p-hydroxy-phenyllactate-esterase activity in laryngeal squamous cell carcinoma.

We assayed methyl-p-hydroxyphenyllactate esterase (MeHPLAase) activity in 63 cases of primary laryngeal squamous cell carcinoma. MeHPLAase activity did not show any correlation with oestrogen, progesterone and epidermal growth factor (EGF) receptor levels. No significant relationship was found between MeHPLAase activity and age, sex, tumour site, T classification, stage of disease and EGFR status, whereas a significant inverse relationship was found between enzymatic activity and neck lymph node positivity at presentation. The median value of MeHPLAase activity tended to be higher in tumours with low histopathological grade than in those with high histopathological grade. During the follow-up period (median 50 months, range 2-90 months) locoregional recurrences were observed in 31 out of 63 (49%) cases. At the end of the study, 27 out of 63 (43%) patients had died of cancer. Cox univariate analysis using MeHPLAase activity as a continuous covariate showed that the levels of enzymatic activity were inversely associated with the risk of death and relapse. Assuming the mean value of enzymatic activity as the cut-off value, we found a statistically significant relationship between high MeHPLAase activity and longer relapse-free and overall survival. MeHPLAase activity status retained its prognostic significance also in the lymph node-negative subgroup of patients. On multivariate analysis, both EGFR and MeHPLAase activity proved to be independent factors for predicting a short relapse and the overall survival.

Morphometric prognostic index in breast cancer.

OBJECTIVE: To assess the ability of the morphometric prognostic index (MPI) in predicting clinical outcome in a group of breast cancer patients with short-term follow-up and to assess the relationship between MPI and other prognosticators. STUDY DESIGN: The study group consisted of 63 cases of breast cancer. Follow-up data were available for 48 patients. MPI values were calculated, and degree of nuclear and tubular differentiation was investigated in each tumor. S-phase fraction (SPF), estrogen and progesterone receptors were also studied. RESULTS: The group of patients with MPI values < 0.60 had percent values of disease-free survival significantly higher than did those with MPI values > or = 0.60. Furthermore, significant direct correlations were found between MPI and degree of nuclear atypia and between MPI and SPF. Significant inverse relationships were found between MPI and tumor progesterone receptor levels and between MPI and degree of histologic tubular differentiation. CONCLUSION: The validity of MPI as a prognosticator in breast cancer was confirmed, even in a limited number of patients observed in short-term follow-up. MPI seems to be a reliable and economical prognosticator in selecting breast cancer patients for adjuvant chemotherapy.