Thymidine phosphorylase expression and stromal vascularity in ductal carcinoma in situ of the breast.(Original Article)

J Clin Pathol 2003;56:919-923

Aims: Periductal angiogenesis in ductal carcinoma in situ is associated with an increased risk of subsequently developing a recurrence. This study aimed to (1) identify the relation between periductal and stromal vascularity and recurrence and (2) determine whether thymidine phosphorylase (TP) is associated with angiogenesis or recurrence in ductal carcinoma in situ (DCIS).

Methods: Twenty cases of DCIS that did not subsequently recur, 20 that developed a subsequent in situ recurrence, and 12 that developed a subsequent invasive recurrence were investigated. Periductal and stromal (hotspot) microvessel density were determined quantitatively using antibodies to CD34 and von Willebrandt factor (vWF). TP expression by DCIS was assessed semiquantitatively using the H score method.

Results: Stromal and periductal microvessel density assessed by anti-vWF gave similar mean values, and showed a strong positive correlation. When angiogenesis was assessed with anti-CD34 this association was lost. Not only were the mean values for both types of microvessel density higher than those obtained with anti-vWF, but the periductal microvessel density was significantly greater than the stromal microvessel density. TP expression was associated with stromal microvessel density assessed with anti-vWF, but not with anti-CD34. TP expression was not related to recurrence. No significant difference was identified in TP expression or stromal vascularity in DCIS between cases that recurred as DCIS and those that recurred as invasive carcinoma.

Conclusions: Recurrent in situ or invasive disease after excision of DCIS does not appear to be related to stromal microvessel density or to TP expression by DCIS cells.

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Since the introduction of the UK National Breast Screening Programme the frequency with which ductal carcinoma in situ (DCIS) is detected has increased from less than 5% to approximately 20% of all carcinomas. (1) DCIS is a non-fatal disease and is potentially curable. However, if following initial treatment recurrent disease develops, then approximately 50% of the recurrences are as invasive carcinoma. (2 3) Although standard histological parameters such as DCIS nuclear grade, size, and the status of the excision margins predict disease recurrence to some extent, (2 3) no factors are known to predict the development of recurrent invasive disease.

There is increasing evidence that angiogenesis has a role as a prognostic factor for invasive breast cancer. (4-9) In DCIS two different vascular patterns have been identified, increased stromal vascular density and an increase in periductal vessels. (10 11) We have previously shown that an increase in microvessel density (MVD) associated with this last pattern is associated with the development of an invasive recurrence. (12)

Thymidine phosphorylase (TP) is thought to play a role in endothelial cell migration and differentiation, (13) and has been shown to be present within DCIS. (14) The aim of our present study was to see whether TP is associated with the increased periductal vascularity previously identified, or with disease recurrence, and to see whether stromal vascularity is as important as periductal vascularity in determining disease recurrence.

MATERIALS AND METHODS

Patients and tumours (table 1)

Records from 355 patients with DCIS in the Merseyside region were examined. Thirty two patients were identified who were known to have subsequently developed recurrent disease, 20 as recurrent DCIS and 12 as recurrent invasive carcinoma. In addition, 20 cases of DCIS with no history of recurrence after initial treatment were retrieved. These 20 cases had similar clinical and histological features, in addition to initial treatment. Histological features included nuclear grade, pathological grade, tumour size, and excision margin (table 1). We used the same cases in our previous study. (12) The original haematoxylin and eosin …