Evidence for a tumour suppressive function of APRG1 in breast cancer.

INTRODUCTION: Deletion mapping studies have shown that genes in the region 3p21.3 are often deleted in epithelial malignancies. Although the regions deleted differ between individual cancers there appears to be a specificity for the type of malignancy produced. As a result this area of chromosome 3 is thought to contain multiple tumour suppressor genes. The present study concentrates on one gene in that region, APRG1. This gene codes for a protein, which has been implicated in cell membrane interactions. The aim was to determine using quantitative PCR whether the levels of this gene were negatively correlated with clinical outcome in breast cancer. METHODS: One hundred and twenty tumour tissues and 33 normal tissues were analyzed. Levels of transcription of APRG1 were determined using real-time quantitative PCR. APRG1 expression was normalized against CK19. Levels of expression were analyzed against staging, nodal involvement, grade, distant metastasis and survival over a 6 year follow up period. RESULTS: Levels of APRG1 mRNA were lower in malignant tissues. They fell further with increasing stage using the TNM classification This became statistically significant when TNM stages 3 and 4 were compared to TNM 1 (p = 0.0046, p = 0.04, t-test). They were lower in those with positive nodes although this did not reach statistical significance. There was a statistically significant reduction in APRG1 in grade 3 tumours cf. grade 1 (p = 0.0081). APRG1 expression was highly negatively correlated with progressive disease: alive with metastasis (p = 0.0069), local recurrence (p = 0.0055), died of breast cancer (p = 0.11), all progressive disease (p = 0.035). CONCLUSION: This study shows a compelling trend for APRG1 transcription levels to be lower in malignant tissues and lower still in those patients who develop progressive disease. There was also a statistically significant difference in APRG1 levels between grade 3 and grade 1 tumours. These results are highly suggestive of APRG1 acting as a tumour suppressor gene.

WNT5A expression in human breast cancer.

UNLABELLED: The Wnt family encodes secreted signaling molecules involved in cell adhesion and, by implication, cell growth. Wnt5a has been shown to behave as a putative oncogene and also as a tumour suppressor gene. This is a reflection of its role within a multi-step pathway and in the variety of ways in which its production can be stimulated or switched off. Wnt genes can be functionally separated into two classes; those that activate the canonical Wnt/beta-catenin pathway and those that activate the Wnt/Ca++ pathway. Wnt5a signals through frizzled receptors and, depending upon which frizzled receptor is present, may activate either pathway. Therefore the observed function of Wnt5a is entirely dependent upon its context, hence the confusion over its role in tumorigenesis. This study examines Wnt5a mRNA expression using RT-PCR in human breast cancer. MATERIALS AND METHODS: One hundred and twenty malignant breast tumours and 33 normal breast tissues were analysed. The levels of transcription of Wnt5a were determined using real-time quantitative PCR. Levels of expression were analysed against staging, nodal involvement, grade, distant metastasis and survival over a 6-year follow-up period. RESULTS: Levels of Wnt5a mRNA were lower in tumours than in normal tissue (mean values: 107 vs. 62.7). They fell further with increasing stage using the Nottingham Prognostic Index. This became statistically significant when NPI3 was compared to normal tissue (p=0.043, t-test). There was a trend towards lower levels of Wnt5a in those with progressive disease, however, this did not reach statistical significance. In patients with ER-negative disease, lower levels of Wnt5a were significantly associated with a worse clinical outcome (p=0.016). CONCLUSION: There is a trend for mRNA levels to be lower in cancerous tissue and lower still in those showing more aggressive behaviour. This is consistent with the hypothesis that Wnt5a is a tumour suppressor gene with potential clinical applications.

Abdominal ganglioneuromas in adults.

Ganglioneuromas are rare tumours of the parasympathetic nervous system. Their definitive diagnosis is made on histological examination. When they arise from the adrenal medulla, their assessment and management are the same as those of other adrenal tumours. We here report 3 cases of ganglioneuromas highlighting important points regarding the radiological assessment, management, decision making and surgical approaches.

Infiltrating fibromatosis of the breast: a potential pitfall.

Mammary fibromatosis is a rare condition. It presents a big dilemma for the clinician, because it mimics breast cancer clinically, radiologically and sometimes cytologically. We report a case of fibromatosis of the breast and highlight the diagnostic difficulties and management.

Choroidal metastasis-the initial presentation of breast carcinoma.

We report a rare case of a breast carcinoma metastasis in the choroid presenting as the initial symptom of the primary disease.

Is dissection of the internerve tissue during axillary lymphadenectomy for breast cancer necessary?

AIMS: The study evaluates the necessity of dissecting the tissue between the long thoracic and thoracodorsal nerves (internerve tissue) during axillary dissection in breast cancer surgery. By reviewing the lymph node yield and the metastatic rate in the internerve tissue, we examine whether the internerve tissue could be left in situ to minimize the risk of nerve injury. METHODS: A prospective study was conducted on 30 consecutive women undergoing axillary lymphadenectomy for breast cancer. The internerve tissue remaining was excised separately after a routine axillary dissection and was examined by the same pathologist. RESULTS: Twenty (67%) of 30 internerve specimens contained lymph nodes; the internerve nodes were positive for carcinoma in three cases (10%). In one case the lymph node in the internerve tissue was the only metastatic node in the axilla. CONCLUSIONS: There is a significant incidence of lymph nodes (67%) and axillary node metastases (10%) in the tissue lying between the long thoracic and thoracodorsal nerves. Therefore excision of this internerve tissue is strongly recommended in order to optimize decision making regarding adjuvant treatment and oucome in women with operable breast cancer.