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1.
Cancer Res ; 76(13): 3965-77, 2016 07 01.
Article in English | MEDLINE | ID: mdl-27325642

ABSTRACT

The stability of markers that identify cancer cells that propagate disease is important to the outcomes of targeted therapy strategies. In human melanoma, conflicting data exist as to whether hierarchical expression of CD271/p75/NGFR (nerve growth factor receptor) marks cells with enriched tumorigenicity, which would compel their specific targeting in therapy. To test whether these discrepancies relate to differences among groups in assay approaches, we undertook side-by-side testing of published methods of patient-derived melanoma xenografting (PDX), including comparisons of tissue digestion procedures or coinjected Matrigel formulations. We found that CD271(-) and CD271(+) melanoma cells from each of seven patients were similarly tumorigenic, regardless of assay variations. Surprisingly variable CD271 expression patterns were observed in the analyses of sibling PDX tumors (n = 68) grown in the same experiments from either CD271(-) or CD271(+) cells obtained from patients. This indicates unstable intratumoral lineage relationships between CD271(-) and CD271(+) melanoma cells that are inconsistent with classical, epigenetically based theories of disease progression, such as the cancer stem cell and plasticity models. SNP genotyping of pairs of sibling PDX tumors grown from phenotypically identical CD271(-) or CD271(+) cells showed large pairwise differences in copy number (28%-48%). Differences were also apparent in the copy number profiles of CD271(-) and CD271(+) cells purified directly from each of the four melanomas (1.4%-23%). Thus, CD271 expression in patient melanomas is unstable, not consistently linked to increased tumorigenicity and associated with genetic heterogeneity, undermining its use as a marker in clinical studies. Cancer Res; 76(13); 3965-77. ©2016 AACR.


Subject(s)
Cell Transformation, Neoplastic/pathology , Melanoma/pathology , Neoplastic Stem Cells/pathology , Nerve Tissue Proteins/metabolism , Receptors, Nerve Growth Factor/metabolism , Animals , Apoptosis , Blotting, Western , Cell Proliferation , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/metabolism , Humans , Melanoma/genetics , Melanoma/metabolism , Mice , Mice, Inbred NOD , Mice, SCID , Neoplastic Stem Cells/metabolism , Nerve Tissue Proteins/genetics , Phenotype , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Receptors, Nerve Growth Factor/genetics , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
2.
Head Neck ; 38(9): 1373-9, 2016 09.
Article in English | MEDLINE | ID: mdl-27014970

ABSTRACT

BACKGROUND: Recommended margins for thick cutaneous melanoma (Breslow thickness >4 mm; T4) have decreased over recent decades. Optimal margins and the role of sentinel node biopsy (SNB) in thick head and neck melanoma remain controversial. METHODS: A single-center review was conducted of patients treated between 2002 and 2012 assessing the impact of excision margins and sentinel lymph node status on locoregional recurrence and melanoma-specific survival (MSS). RESULTS: One hundred eight patients were identified. Median age was 71.1 years and median Breslow thickness was 6.0 mm. Median follow-up was 40 months. Locoregional recurrence occurred in 27% and there was no significant reduction in recurrence with margins ≥2 cm (p = .17). Increasing margins did not improve survival (p = .58). Fifty-nine patients (55%) underwent SNB, of which 27% were positive. There was a trend toward longer survival for patients who were sentinel lymph node-negative (p = .097). CONCLUSION: Wider margins do not significantly improve locoregional recurrence or MSS. Sentinel lymph node involvement reflects a poor prognosis. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1373-1379, 2016.


Subject(s)
Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/surgery , Margins of Excision , Melanoma/pathology , Melanoma/surgery , Sentinel Lymph Node/pathology , Skin Neoplasms/pathology , Skin Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Australia , Cancer Care Facilities , Cohort Studies , Disease-Free Survival , Female , Head and Neck Neoplasms/mortality , Humans , Male , Melanoma/mortality , Middle Aged , Prognosis , Retrospective Studies , Risk Assessment , Sentinel Lymph Node/surgery , Sentinel Lymph Node Biopsy/methods , Skin Neoplasms/mortality , Survival Analysis , Treatment Outcome , Young Adult , Melanoma, Cutaneous Malignant
6.
Australas J Dermatol ; 49(1): 52-4, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18186851

ABSTRACT

A 67-year-old Caucasian woman presented with an area of alopecia over the right occipital scalp, which had slowly expanded over the last 10 years. The skin beneath the alopecia felt soft and boggy although the epidermis looked unremarkable. Ultrasound showed thickening of the underlying subcutaneous tissue. Scalp histology showed enlarged fat lobules within the subcutis that infiltrated along fibrous tracts into the mid-dermis. There was a complete loss of hair follicles. These findings were consistent with lipoedematous alopecia of the scalp. Surgical debulking with scalp reduction produced an acceptable result in our patient with no evidence of relapse after 12 months.


Subject(s)
Alopecia/surgery , Scalp Dermatoses/surgery , Scalp/surgery , Skin/pathology , Subcutaneous Fat/surgery , Aged , Alopecia/pathology , Female , Fibrosis/pathology , Humans , Scalp/pathology , Scalp Dermatoses/pathology , Subcutaneous Fat/pathology
7.
J Plast Reconstr Aesthet Surg ; 60(6): 631-4, 2007.
Article in English | MEDLINE | ID: mdl-17485050

ABSTRACT

UNLABELLED: Sentinel lymph node biopsy for malignant melanoma has been performed as day surgery at our hospital since August 2002. The aim of this retrospective study was to assess its feasibility compared to the inpatient procedure. METHODS: A telephone survey and review of medical records was carried out for patients who had daycase, nonhead and neck sentinel lymph node biopsy for malignant melanoma over an 18-month period. A similar matched number of inpatients were reviewed, comparing waiting times, prolonged hospital stay, complication rates and overall satisfaction. RESULTS: There were no significant differences between the two groups in terms of time from diagnosis to surgery, prolonged hospital stay and complication rates. However, in terms of overall satisfaction, 86.3% of daycase patients preferred their mode of admission whereas 52.9% of inpatients preferred their mode of admission (P=0.0003). CONCLUSIONS: Sentinel lymph node biopsy (nonhead and neck) for malignant melanoma as day surgery is feasible and confers greater patient satisfaction, increased availability of inpatient beds and cost savings without compromising patient care.


Subject(s)
Ambulatory Surgical Procedures/methods , Melanoma/diagnosis , Sentinel Lymph Node Biopsy/methods , Skin Neoplasms/diagnosis , Feasibility Studies , Humans , Length of Stay , Patient Satisfaction , Postoperative Complications , Retrospective Studies , Time Factors
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