There is more than one kind of myofibroblast: analysis of CD34 expression in benign, in situ, and invasive breast lesions

Abstract

Aims: Smooth muscle actin (SMA) positive myofibroblasts have been implicated in tumour invasion; however, acquisition of SMA is not limited to peritumorous fibroblasts and other changes in fibroblasts may be more specifically related to the malignant environment. CD34 is a sialomucin expressed by normal breast fibroblasts but lost in invasive carcinomas. The aim of this study was to establish the relation between CD34 and SMA expression in breast fibroblasts and to analyse whether loss of CD34 is specific for invasive disease. Methods: Immunohistochemistry for CD34 and SMA was performed on 135 cases including 10 normal, 10 fibroadenomas, 40 infiltrating ductal carcinomas, 55 cases of ductal carcinoma in situ (DCIS), and 20 radial scar/complex sclerosing lesions. The relation between staining pattern and histopathological features was recorded as positive, negative, or reduced. Results: Fibroblasts around all normal duct-lobule units and those showing epithelial hyperplasia were CD34 positive and mainly SMA negative. In fibroadenomas, fibroblasts retained CD34 but acquired SMA expression. In contrast, fibroblasts around invasive carcinoma were CD34 positive and SMA negative. In DCIS, loss of CD34 was significantly more frequent in high grade tumours than in low or intermediate grade ones (p < 0.001). The acquisition of SMA was seen more frequently than the loss of CD34, particularly in non-high grade DCIS. In all radial scars, fibroblasts were SMA positive but CD34 negative, and a similar pattern was seen in stromal cells in areas of fibrosis following core biopsy. Conclusions: These results show that SMA positive myofibroblasts exhibit variable expression of CD34, indicating that these markers are not coordinately controlled. Loss of CD34 is strongly related to the malignant phenotype, in both invasive and preinvasive disease, but is not entirely specific because radial scar fibroblasts and fibroblasts in reactive fibrosis exhibit a similar phenotype. The functional relevance of altered CD34 expression is unclear but the very focal changes implicate local signalling mechanisms probably of epithelial origin.T here is increasing evidence to indicate that the tumour microenvironment exerts a major modulatory effect on epithelial tumours and that the stroma makes an important contribution to the process of tumour progression.

Distribution and significance of nerve growth factor receptor (NGFR/p75NTR) in normal, benign and malignant breast tissue

“…In all samples, myofibroblasts showed strong and diffuse immunoreactivity for NGFR, with a distribution similar to that described for CD34 39 (Figure 3a and b).…”

“…19,21 In the stromal compartment of normal breast and benign and malignant breast lesions, the distribution of NGFR is strikingly similar to that described for CD34. 39,45,46 In fact, NGFR was consistently expressed by intralobular (myo)fibroblasts, stromal cells of benign biphasic neoplasms and in pseudoangiomatous stromal hyperplasias, but largely negative in the stromal compartment of invasive tumours. 39,45 Our findings corroborate those of Chauhan et al, 39 giving further evidence for the existence of more than one type of fibroblast in normal breast and in the stromal compartment of breast lesions.…”

“…Similar expression patterns have been observed with other stromal markers, such as CD34. 39,47 Interestingly, the expression pattern of these markers has been linked with the clinical behaviour of these lesions. 47,48 Further studies analysing a large series of biphasic tumours of the breast are warranted.…”

Myoepithelial markers are expressed in at least 29% of oestrogen receptor negative invasive breast carcinoma

“…8,37 In this respect, recent studies have suggested the existence of more than one type of myofibroblasts in breast lesions, which vary in their expression of smooth muscle actin and CD34. 38 It has to be added here, that it would be interesting to compare the staining results of the recently introduced nuclear myoepithelial cell marker p63 39 with the more established cytoplasmic markers for these cells in a future study.…”

Evaluating the Expression of CD34 Marker in Colorectal Adenocarcinoma and its Relationship with Clinicopathologic Factors

“…The expression of this marker is lost in invasive breast carcinoma. This loss is attributed to the malignant phenotype and although the role of expression change is not clarified but it shows the regional messaging mechanisms with epithelial origin (Chauhan et al, 2003).…”