The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial.

BACKGROUND: Previous data suggest that the immune microenvironment plays a critical role in human epidermal growth factor receptor 2 (HER2) -positive breast cancer; however, there is little known about the immune profiles of small HER2-positive tumors. In this study, we aimed to characterize the immune microenvironment of small HER2-positive breast cancers included in the Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer (APT) trial and to correlate the immune markers with pathological and molecular tumor characteristics. PATIENTS AND METHODS: The APT trial was a multicenter, single-arm, phase II study of paclitaxel and trastuzumab in patients with node-negative HER2-positive breast cancer. The study included 406 patients with HER2-positive, node-negative breast cancer, measuring up to 3 cm. Exploratory analysis of tumor infiltrating lymphocytes (TIL), programmed death-ligand 1 (PD-L1) expression (by immunohistochemistry), and immune gene signatures using data generated by nCounter PanCancer Pathways Panel (NanoString Technologies, Seattle, WA), and their association with pathological and molecular characteristics was carried out. RESULTS: Of the 406 patients, 328 (81%) had at least one immune assay carried out: 284 cases were evaluated for TIL, 266 for PD-L1, and 213 for immune gene signatures. High TIL (≥60%) were seen with greater frequency in hormone-receptor (HR) negative, histological grades 2 and 3, as well in HER2-enriched and basal-like tumors. Lower stromal PD-L1 (≤1%) expression was seen with greater frequency in HR-positive, histological grade 1, and in luminal tumors. Both TIL and stromal PD-L1 were positively correlated with 10 immune cell signatures, including Th1 and B cell signatures. Luminal B tumors were negatively correlated with those signatures. Significant correlation was seen among these immune markers; however, the magnitude of correlation did not indicate a monotonic relationship between them. CONCLUSION: Immune profiles of small HER2-positive breast cancers differ according to HR status, histological grade, and molecular subtype. Further work is needed to explore the implication of these findings on disease outcome. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00542451.

A systematic review of factors that influence treatment adherence in paediatric oncology patients.

WHAT IS KNOWN AND OBJECTIVE: Treatment adherence is an essential component in ensuring best outcomes in the management of paediatric cancers. Compared to the adult population, treatment adherence in the paediatric population is a more complex subject which involves unique dimensions. In this study, we aimed to systematically review the literature to identify factors associated with treatment adherence in the paediatric oncology population. METHODS: A literature search was carried out using related keywords on electronic databases. RESULTS AND DISCUSSION: A total of 1036 articles were reviewed, and 39 articles were found to be relevant. A comprehensive review of these articles identified 17 factors that influence adherence. These factors were classified into five major categories: patient-/caregiver-related factors; therapy-related factors; condition-related factors; health system-related factors; and social/economic factors. A baby bear model was proposed to better visualize these five categories that affect treatment adherence, and a framework of questions was designed to help clinicians identify those at risk of non-adherence for early intervention. WHAT IS NEW AND CONCLUSION: Seventeen factors reviewed were categorized into five main categories, namely patient-/caregiver-related factors, therapy-related factors, condition-related factors, health system factors and social/economic factors, as causes for poor medication adherence in the paediatric oncology population. Clinicians need to be aware that these factors can interact to influence treatment adherence and that some factors may be more relevant in specific contexts (e.g. third world countries, minority groups). The baby bear model is presented to help understand the issues affecting adherence in the paediatric oncology population, and a framework of questions is proposed to help clinicians identify patients at risk of non-adherence.

Effects of parathyroid hormone and estradiol on proliferation and function of human osteoblasts from fetal long bone. An in vitro study.

The effect of parathyroid hormone (PTH) (0.01 nM-10 nM) and 17 beta-estradiol (E2, 1 nmol-10 nM) alone or in combination on 3H-thymidine incorporation, alkaline phosphatase and adenylate cyclase activities were investigated in human fetal osteoblasts using serum-free monolayer primary cultures. The results showed that PTH inhibited cell proliferation while E2 promoted it. On alkaline phosphatase activity, PTH showed a complex results while E2 were slightly inhibitory. PHT-E2 combination suggested that E2 could alter the effect of PTH alone, also potentiated the anabolic and antagonize the catabolic effects of PTH on bone formation.

[Changes in neuroendocrine cells and immunocompetent cells in bronchiectasis].

Pulmonary endocrine cells and immunocompetent cells from the lungs of 35 subjects with bronchiectasis and in 10 normal controls were investigated by using immunohistochemical technique. The morphological and immunohistochemical characteristics of bronchus associated lymphoid tissue (BALT) of the lung were also studied. The number of calcitonin and serotonin immunoreactive pulmonary endocrine cells increased significantly in bronchiectasis as compared with those from control subjects. The number of IgA, IgG and IgM positive cells and UCHL1 positive cells were higher in the bronchial lamina propria in bronchiectasis than those in controls. These changes were most marked in hyperplastic BALT areas, which suggest that neuroendocrine and immune mechanisms may be involved in the pathogenesis of bronchiectasis.

[The diagnosis of uterine leiomyosarcoma and endometrial stromal sarcoma].

The diagnostic problems in uterine smooth muscle tumors and endometrial stromal tumors are reviewed and discussed with analysis of 14 selective cases collected from the affiliated hospital. Data suggested that, in the differential diagnosis of benign and malignant uterine smooth muscle tumors, it is not comprehensive to use mitotic activity as the only criterion. Nuclear atypia and some other clinico-pathological features should be considered together, and, it is important to recognize the "mitotic active" leiomyoma which runs a benign course despite a high mitotic rate. In endometrial stromal sarcoma, the growth pattern and the extent of tumor spreading seem not closely correlated with the mitotic activity, nor the atypia, and, the clinical stage was considered as a significant reference in the prognosis. Thus, it is suggested that the differentiation of endometrial stromal sarcoma into low and high malignancy according to the mitotic rate alone is not the best reliable guide in evaluating the tumor behavior. It is emphasized that the extent of spreading of the tumor should be stated in the diagnosis. Immunohistochemical study revealed that the sex cord element in endometrial stromal sarcoma and other uterine tumors expressed a myogenous rather than an epithelial phenotype.

[Morphogenetic study on hyperplastic and neoplastic diseases of endocrine pancreas].

A morphologic study was conducted on nesidioblastosis, islet cell hyperplasia, adenomatous hyperplasia of islets of Langerhans and true islet cell adenoma with histochemical, immunohistochemical, electron microscopic and morphometric techniques. The results showed that the morphologic features of these four diseases were correlated with the development of pancreas and to a certain extent duplicated the process of fetal development. These findings seem to support the hypothesis that there exists a full spectrum of conditions ranging from the original nesidioblastosis to islet cell hyperplasia, adenomatosis and true islet cell adenoma.

[Immunohistochemical study and lectin distribution of thyroid carcinoma originated from follicular epithelium].

97 cases of thyroid carcinoma originated from follicular epithelium were investigated by using histological and immunohistochemical techniques with special reference to lectin distribution. According to the WHO histological typing of thyroid tumours, these cases were divided into three categories as follows: papillary carcinoma of thyroid (PCT) 56, follicular carcinoma of thyroid (FCT) 31 and undifferentiated carcinoma of thyroid (UCT) 10. Results showed that three different kinds of thyroid carcinoma presented various hormone function and distribution of lectins. The positive rate of Tg immunoreactivity was significantly different between these three kinds of tumour, i.e. PCT greater than FCT greater than UCT. Additionally, the positive rate of T4 and T3 immunoreactivity was lower than that of Tg. Some Gastrin, SS and calcitonin positive cells were also recognized in carcinoma of thyroid. Lectin--binding rate of WGA, PNA, SBA and UEA to 97 cases of thyroid carcinoma and 9 cases of normal thyroid tissue revealed that different lectin had a selective binding activity to various types of thyroid carcinoma and normal thyroid cells. From the data obtained, it seemed that the morphological differentiation of thyroid carcinoma was in correspondence with difference of function, and the extent of cell differentiation may be closely related to the biological behavior of the tumour.

Gossypol acetate-induced SCEs in spermatogonia and bone marrow cells of mice: dose-response relationships.

Gossypol acetic acid has been shown to have the effect of increasing the SCE frequencies in the spermatogonial cells of mice. This study further confirmed the genotoxic effects of gossypol acetic acid by investigating the dose-response relationships of gossypol acetic acid-induced SCEs in spermatogonial cells and bone marrow cells of mice. Twelve or over 12 mg/kg body weight of the dosage per day could increase the SCE frequencies of both bone marrow cells and spermatogonial cells. The increase of SCE frequency appeared to be directly correlated with the doses used at significant levels (p less than 0.001). Regression lines indicated that, in spite of cell type variation, the SCE induced was proportional to the dose of gossypol acetic acid.