Changes in angiogenesis and hypoxia-inducible factor-1α protein expression in relapsed/refractory indolent non-Hodgkin lymphomas.

Angiogenesis is involved in the pathogenesis and progression of non-Hodgkin lymphomas (NHL), and hypoxia-inducible factor-1α (HIF-1α, also termed HIF1A) might contribute to this process. Currently, there is no direct evidence that the clinical progression of indolent NHL is associated with angiogenesis, and the expression of HIF-1α at recurrence is unknown. Matched lymph node biopsies at diagnosis and recurrence of relapsed/refractory indolent NHL patients were analysed by immunohistochemical and morphometric analysis. We observed an increased vascular network and HIF-1α protein expression in the second biopsy, providing direct evidence that angiogenesis is an essential process for disease progression.

Morphological parameters of lobular in situ neoplasia in stereotactic 11-gauge vacuum-assisted needle core biopsy do not predict the presence of malignancy on subsequent surgical excision.

AIMS: The management of lobular in situ neoplasia (LN) when diagnosed on core biopsy remains a controversial issue. The present study aimed to investigate the association between morphological parameters of LN on vacuum-assisted needle core biopsy (VANCB) and the presence of malignancy (ductal carcinoma in situ, pleomorphic lobular carcinoma in situ, or invasive carcinoma) at surgical excision (SE). METHODS AND RESULTS: The study included 14 pathology departments in Italy. Available slides from 859 cases of VANCB reporting an original diagnosis of flat epithelial atypia, atypical ductal hyperplasia or LN, all with subsequent surgical excision, were reviewed. Overall, 286 cases of LN, pure or associated with other lesions, were identified, and a malignant outcome was reported at excision for 51 cases (17.8%). Among the 149 cases of pure LN, an increased risk of malignancy emerged in women in mammographic categories R4-R5 as compared with those in categories R2-R3 (OR 2.46; P = 0.048). In the series, a statistically significant decreased malignancy risk emerged among cases without determinant microcalcifications (P = 0.04). CONCLUSIONS: Our results suggest that the diagnosis of pure LN on VANCB warrants follow-up excision, because clinicopathological parameters do not allow the prediction of which cases will present carcinoma at surgical excision.

Centromere 17 copy number alteration: negative prognostic factor in invasive breast cancer?

CONTEXT: Chromosome 17 polysomy has been identified in 5% to 50% of invasive breast cancers; even though a relationship with human epidermal growth factor receptor 2 (HER2/ neu ) status has been reported, other studies have shown that coincident centromere 17 (Cep17) amplification may be the cause of an overestimation of chromosome 17 polysomy in fluorescence in situ hybridization (FISH) testing. OBJECTIVE: To evaluate polysomy/amplification of Cep17 in invasive breast cancer with relation to proliferative activity (Ki-67), estrogen receptor, progesterone receptor, and HER2/ neu status, in an attempt to identify a subgroup of patients with a worse prognosis. DESIGN: A total of 647 cases of invasive ductal breast cancer were collected and subjected to FISH analysis for HER2/neu gene and centromere 17 alteration, HercepTest for HER2/ neu protein expression, and routine immunohistochemistry for Ki-67 and hormone receptor status. RESULTS: Copy number gain of Cep17 was observed in 27.3% of cases. Within this group, HER2/neu gene amplification was detected in 14.1% of cases, whereas HER2/ neu expression was scored 3+ in 20.1% of cases; about half of the HER2/ neu overexpressing cases (9.8%) did not show amplification by FISH. Moreover, 69% of polysomic cases showed high Ki-67 index. CONCLUSIONS: (1) Centromere 17-altered cases are frequently HER2/ neu overexpressing but not amplified, resulting in HercepTest/FISH disagreement; (2) HER2/neu amplification is seen at a higher incidence in cases without Cep17 copy number alterations, which are therefore not necessarily due to chromosome 17 disorder; (3) proliferation index is significantly higher in aneusomic tumors. These data suggest that the presence of Cep17 alterations could identify a subset of breast cancers with more aggressive biological and clinical behavior, which may show nonresponsiveness to conventional therapy independently of HER2/neu amplification status.

Morphological parameters of flat epithelial atypia (FEA) in stereotactic vacuum-assisted needle core biopsies do not predict the presence of malignancy on subsequent surgical excision.

Flat epithelial atypia (FEA) may represent the earliest precursor of low-grade breast cancer and often coexists with more advanced atypical proliferative breast lesions such as atypical ductal hyperplasia (ADH) and lobular intraepithelial neoplasia (LIN). The present study aims to investigate the association between morphological parameters of FEA and presence of malignancy at surgical excision (SE) and the clinical significance of the association of FEA with ADH and/or LIN. This study included 589 cases of stereotactic 11-gauge vacuum-assisted needle core biopsy (VANCB), reporting a diagnosis of FEA, ADH or LIN with subsequent SE from 14 pathology departments in Italy. Available slides were reviewed, with 114 (19.4 %) showing a malignant outcome at SE. Among the 190 cases of pure FEA, no statistically significant association emerged between clinical-pathological parameters of FEA and risk of malignancy. Logistic regression analyses showed an increased risk of malignancy according to the extension of ADH among the 275 cases of FEA associated with ADH (p = 0.004) and among the 34 cases of FEA associated with ADH and LIN (p = 0.02). In the whole series, a statistically significant increased malignancy risk emerged according to mammographic R1-R3/R4-R5 categories (OR = 1.56; p = 0.04), extension (OR = 1.24; p = 0.04) and grade (OR = 1.94; p = 0.004) of cytological atypia of FEA. The presence of ADH was associated with an increased malignancy risk (OR = 2.85; p < 0.0001). Our data confirm the frequent association of FEA with ADH and/or LIN. A diagnosis of pure FEA on VANCB carries a 9.5 % risk of concurrent malignancy and thus warrants follow-up excision because none of the clinical-pathological parameters predicts which cases will present carcinoma on SE.

Serum vascular endothelial growth factor and adiponectin levels in patients with benign and malignant gynecological diseases.

INTRODUCTION: One of the most specific and critical regulators of angiogenesis is vascular endothelial growth factor (VEGF), which regulates endothelial proliferation, permeability, and survival. Vascular endothelial growth factor is an angiogenic mediator in tumors and has been implicated in the pathogenesis and progression of cancer. Adipose tissue is a major endocrine and it secretes hormones termed adipokines. These factors are derived from adipocytes and include proteins and metabolites such as adiponectin. Recently, adiponectin was also shown to modulate angiogenesis. This study was designed to determine the serum VEGF and adiponectin levels in patients with benign and malignant gynecological diseases and if there was a correlation between serum VEGF and adiponectin. METHODS: Serum samples, collected fasting before surgery or intervention, were available for total of 114 female patients recorded between October 2006 and December 2008. Diagnosis of benign and malignant gynaecological diseases was established by biopsy. Serum levels VEGF and adiponectin were using commercially available enzyme linked immunosorbent assay (R&D Systems Inc, Minneapolis, MN), respectively. Statistical analysis was performed by using the SPSS 9.0 software package (SPSS, Inc, Chicago, IL). The correlation between serum VEGF and serum Adiponectin was calculated using the Pearson correlation coefficient. P values of < 0.05 were considered statistically significant. RESULTS: Our results were analyzed on the basis of 2 different parameters: age and benign and malignant gynecological diseases of the patient. Only for serum VEGF levels was a significant difference observed (P = 0.004) between patients with benign and malignant gynecological diseases. A significantly inverse correlation between serum VEGF and adiponectin levels among patients with benign and malignant gynecological diseases was found. Adiponectin level is not correlated with body mass index. CONCLUSIONS: This is one of the first report on adiponectin in benign and malignant gynecological diseases. Future studies are needed to address the clinical potential role of adiponectin in cancer.