Kerstin J. Rolfe

TP53 mutations in vulval lichen sclerosus adjacent to squamous cell carcinoma of the vulva

Non-neoplastic epithelial lesions of the vulva (NNEDV) lichen sclerosus (LS) and squamous hyperplasia (SH) have been implicated in the pathogenesis of squamous cell carcinoma of the vulva (SCC). To date, there have been no recognisable precursor lesions for SCC associated with NNEDV. TP53 is the most frequent genetic change in human cancers and can indicate both aetiology and molecular pathogenesis of tumours. A total of 27 SCC patients underwent immunohistochemistry (IHC) and TP53 mutational analysis using microdissection and direct sequencing. There were 19 patients with areas of adjacent epidermis: 17 had NNEDV (four SCCs had more than one adjacent lesion) and two had normal epidermis. In all, 70.4% of the SCCs, 40% LS and 22.2% SH demonstrated overexpression of p53. In total, 77.8% of SCCs, 46.7% of LS and 22.2% SH demonstrated mutations in TP53, with the majority of lesions having a mutation in codon 136. Eight cases were identified where the same mutation was identified in the SCC and in the adjacent area. These data suggest that TP53 mutations develop in NNEDV and are intrinsic to the clonal evolution that leads to SCC. The type of mutation detected is more likely to occur due to endogenous cellular changes rather than exogenous carcinogen exposure.

Estrogen receptor expression in vulvar vestibulitis syndrome

OBJECTIVE A pilot study was performed to investigate the relationship between vulvar vestibulitis syndrome and estrogen receptor expression. STUDY DESIGN Women with a diagnosis of vulvar vestibulitis syndrome had tissue samples taken for vulvar estrogen receptor-alpha expression and this was compared with a control group. RESULTS The study group showed a significant decrease in estrogen receptor expression, and 50% of the samples did not exhibit any receptor expression. CONCLUSION There appears to be a subgroup of women with vulvar vestibulitis syndrome who exhibit abnormal estrogen receptor-alpha expression. This may be helpful in explaining why some women are resistant to medical treatment and may allow treatment to be prescribed more effectively.

A Review of Fetal Scarless Healing

Wound healing is a complex process involving a number of processes. Fetal regeneration has been shown to have a number of differences compared to scar-forming healing. This review discusses the number of differences identified in fetal regeneration. Understanding these differences may result in new therapeutic targets which may reduce or even prevent scarring in adult healing.

The growth factors involved in flexor tendon repair and adhesion formation

Flexor tendon injuries remain a significant clinical problem, owing to the formation of adhesions or tendon rupture. A number of strategies have been tried to improve outcomes, but as yet none are routinely used in clinical practice. Understanding the role that growth factors play in tendon repair should enable a more targeted approach to be developed to improve the results of flexor tendon repair. This review describes the main growth factors in tendon wound healing, and the role they play in both repair and adhesion formation.

In Vitro Flexor Tendon Cell Response to TGF-β1: A Gene Expression Study

PURPOSE Adhesion formation around zone II flexor tendon repairs remains an important clinical challenge. Tendon healing is complex, and when uncontrolled it may lead to adhesion formation. Transforming growth factor-beta1 (TGF-beta1) is a multipotent growth factor known to be involved in wound healing and scar formation. It has also been shown to have a role in both tendon healing and adhesion formation. METHODS Uninjured rabbit flexor tendons were divided into endotenon, epitenon, and sheath cells and cultured separately. The in vitro effect of TGF-beta1 gene expression was determined on quiescent tendon cells using real-time polymerase chain reaction for collagen type 1, collagen type 3, fibronectin, plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (t-PA). RESULTS Endotenon-derived cells showed a statistically significant down-regulation of collagen type I gene expression in response to TGF-beta1 compared with untreated endotenon cells and with both epitenon and sheath cells at a number of time points. However, endotenon cells showed an increase in collagen type 3 gene expression compared with untreated cells and epitenon cells. All cells showed a statistically significant increase in fibronectin in the later time points compared with the untreated cells. Endotenon-derived cells showed an early increase in PAI-1, whereas sheath cells showed a later increase. CONCLUSIONS We have shown that cells cultured from 3 separate parts of the flexor tendon-sheath complex respond in different ways when stimulated with TGF-beta1. The down-regulation of collagen types 1 and 3 in endotenon cells may give further insight into the effects of TGF-beta1 in tendon healing. Also, the upregulation of fibronectin and PAI-1, combined with a down-regulation of tissue plasminogen activator, could explain the association of TGF-beta1 with tendon adhesion formation. Treatments aimed at improving tendon healing and the prevention of adhesions may arise from modification of the effects of TGF-beta1.

Ovarian cancer and infertility: a genetic link?

A genetic mechanism may be responsible for the increased incidence of ovarian cancer in some infertile women (ie, those who failed to conceive despite treatment).

Expression of cyclin D1 and retinoblastoma protein in Paget's disease of the vulva and breast: an immunohistochemical study of 108 cases.

Aims:  Loss of retinoblastoma protein expression and overexpression of cyclin D1 have been implicated in the development and progression of some cancers. Paget’s disease of the vulva (PDV) and Paget’s disease of the breast (PDB) are uncommon conditions and the pathogenesis of these diseases is still unclear. The aim was to examine the expression of the retinoblastoma and cyclin D1 proteins in PDV and PDB and to correlate any differences between PDV and PDB, and in the presence or absence of an underlying carcinoma.

The attachment of intrinsic and extrinsic, mobilized and immobilized adhesion cells to collagen and fibronectin

This study investigated the attachment of intrinsic and extrinsic, mobilized and immobilized adhesion cells to the extracellular matrix. Five New Zealand White rabbit forepaws were dissected to isolate the flexor tendon core, tendon surface and synovial sheath, which were explanted separately. A further 10 animals were subjected to flexor tendon injuries, randomized to either mobilization or immobilization, and adhesions were explanted at 2 weeks. Cell groups were tested for attachment to collagen type-I or fibronectin and morphometric analysis was made. The attachment of intrinsic tendon cells and adhesion cells from mobilized tendons to both matrix proteins was statistically significantly greater than that of extrinsic tendon cells and adhesion cells from immobilized tendons. Adhesion cells from mobilized tendons were statistically significantly more elongated, which may correlate with the deposition of a more organized matrix. Because the synovial sheath cells were least attached to matrix proteins, selective treatments that reduce cell attachment may be used to exclude them, without inhibiting intrinsic tendon healing.