mRNA expression of DOK1-6 in human breast cancer

AIM:To examine the expression of downstream of tyrosine kinase(DOK)1-6 genes in normal and breast cancer tissue and correlated this with several clinicopathological and prognostic factors.METHODS:DOK1-6 m RNA extraction and reverse transcription were performed on fresh frozen breast cancer tissue samples(n = 112) and normal background breast tissue(n = 31). Tissues were collected between 1991 and 1996 at two centres and all patients underwent mastectomy and ipsilateral axillary node dissection. All tissues were randomly numbered and the details were only made known after all analyses were completed. Transcript levels of expression were determined using real-time polymerase chain reaction and analyzed against TNM stage, tumour grade and clinical outcome over a 10-year follow-up period.RESULTS:DOK-2 and DOK-6 expression decreased with increasing TNM stage. DOK-6 expression decreased with increasing Nottingham Prognostic Index(NPI) [NPI-1 vs NPI-3(mean copy number 15.4 vs 0.22, 95%CI:2.7-27.6, P = 0.018) and NPI-2 vs NPI-3(mean copy number 7.6 vs 0.22, 95%CI:0.1-14.6, P = 0.048)]. After a median follow up period of 10 years, higherlevels of DOK-2 expression were found among patients who remained disease-free compared to those who developed local or distant recurrence(mean copy number 3.94 vs 0.0000096, 95%CI:1.0-6.85, P = 0.0091), and distant recurrence(mean copy number 3.94 vs 0.0025, 95%CI:1.0-6.84, P = 0.0092). Patients who remained disease-free had higher levels of DOK-6 expression compared to those who died from breast cancer.CONCLUSION:Decreasing expression levels of DOK-2 and DOK-6 with increased breast tumour progression supports the notion that DOK-2 and DOK-6 behave as tumour suppressors in human breast cancer.

Evidence for Tumour Suppressor Function of DOK7 in Human Breast Cancer

Introduction: Downstream of tyrosine kinase 7 (DOK-7) is a member of the DOK family, which has been associated with the development and progression of various humancancers. Previously, identification of CpG hypermethylation in DOK-7 promoter was identified in breast cancer. Method: DOK-7 mRNA extraction and reverse transcription were performed on fresh frozen breast cancer tissue samples and normal background breast tissue. Transcript levels of expression were analyzed against TNM stage, tumour grade and clinical outcome over a 10-year follow-up period. Results: Levels of DOK-7 expression decreased significantly with increasing TNM stage. Higher DOK-7 expression was correlated with longer disease free and overall survival times. Conclusion: To our knowledge, this is the first study to investigate DOK-7 expression in human breast cancer. We identify a potential DOK-7 tumour suppressor role. DOK-7 as a prognostic biomarker in human breast cancer should be included in future validation studies.

Evolving role of skin sparing mastectomy

Skin sparing mastectomy(SSM) can facilitate immediate breast reconstruction and is associated with an excellent aesthetic result. The procedure is safe in selected cases; including invasive tumours < 5 cm, multi-centric tumours, ductal carcinoma in situ and for risk-reduction surgery. Inflammatory breast cancers and tumours with extensive involvement of the skin represent contraindications to SSM due to an unacceptable risk of local recurrence. Prior breast irradiation or the need for post-mastectomy radiotherapy do not preclude SSM, however the aesthetic outcome may be compromised. Preservation of the nipple areola complex is safe for peripherally located node negative tumours. An intraoperative frozen section protocol for the retro-areolar tissue should be considered in these cases. The advent of acellular tissue matrix systems has enhanced the scope of implant-based immediate reconstruction following SSM. Cell-assisted fat transfer is emerging as a promising technique to optimise the aesthetic outcome.

Skin-Sparing Mastectomy and Breast Reconstruction: An Update for Clinical Practice

Aim: To provide an up-to-date review of the literature on skin-sparing mastectomy (SSM) for breast cancer (BC). The article also reviews the oncological safety, effects of radiotherapy (RT) on immediate breast reconstruction (IBR), the indications for preserving the nipple-areola complex (NAC) and the emerging role of allogenic grafts as adjuncts to implant in IBR. Methods: Review of the English literature from 1965 to 2013 was carried out using Medline and PubMed research engines. Results: SSM is oncologically safe in appropriately selected cases of invasive breast cancer (IBC) and ductal carcinoma in-situ (DCIS) including IBC 5 cm, multi-centric tumours, DCIS and for risk-reduction surgery. Inflammatory breast cancer and tumours with extensive skin involvement represent contra-indications to SSM due to an unacceptable risk of local recurrence. Prior breast irradiation or the need for post-mastectomy radiotherapy (PMRT) do not preclude SSM with IBR, however the aesthetic outcome may be compromised by radiation. Preservation of the nipple-areola complex (NAC) has aesthetic and psychological benefits and is safe for peripherally located node negative unifocal tumours. An intraoperative frozen section protocol for the retro-areolar tissue should be performed when NAC preservation is considered. The advent of acellular dermal matrix has enhanced the scope of implant-based immediate reconstruction following SSM. Cell-assisted fat transfer is emerging as a promising technique to optimise the aesthetics outcome. There is no sufficient evidence to support the role of endoscopic mastectomy in clinical practice. Conclusion: Numerous retrospective and prospective studies show that SSM is oncolgically safe in appropriately selected cases and is aesthetically superior to non-SSM mastectomy. New tech-niques such as the use of acellular dermal matrix (ADM) and cell-assisted fat transfer have increased the use of implants for volume replacement following SSM. In the absence of randomized clinical trials, an updated systematic meta-analysis of published studies is required in order to consolidate the evidence.