Tumour-associated eosinophilia has been observed in human cancers, sometimes with different results regarding their association with clinical outcome [6-11].

Mast cells derive from a specific bone marrow progenitor cell and migrate into tissues where they mature depending on the microenvironmental conditions.

Mast cells may promote tumour development through many different ways. Mast cells could facilitate tumour angiogenesis through heparin-like molecules and heparin could further permit neovascularisation and metastases through its anti-clotting effects [12]. Moreover, mast cells secrete histamine and growth factors, such as VEGF (vascular endothelial growth factor), PDGF (platelet derived growth factor), SCF (stem cell factor) and NGF (nerve growth factor). Mast cells are also rich in metalloproteases that contribute to the majority of proteolytic components necessary for tumour invasiveness [3]. On the other hand, mast cells could also be detrimental to tumour growth by secreting several cytokines and proteolytic enzymes participating in inducing apoptosis of the malignant cells, such as IL-4 [13]. The dual role of mast cells in inhibiting or promoting tumour growth needs to be further investigated [14]. Few studies of stromal mast cells in invasive breast carcinomas have been done and two previous studies have indicated that many stromal mast cells are correlated to a favourable prognosis [15-17]. Furthermore, in lymph nodes of women with breast cancer a higher number of mast cells were found in the non-involved axillary lymph nodes in those women with a better prognosis [18]. In women with axillary lymph node metastasis more mast cells were found in the non-involved axillary lymph nodes [19]. These findings might indicate a protective effect of mast cells, possibly exerting a cytotoxic effect on the tumour cells. However, the studies are still few and further investigations are needed in order to elucidate the precise role of mast cells in the tumourigenesis. Mast cells interact with eosinophils in bidirectional interactions and cytokine networks [20]. Eosinophils may serve as a source of SCF which induces the growth of mast cells regulating their activation, degranulation and chemotaxis.

In Hodgkin lymphomas, many eosinophils in the tumours are correlated to an unfavourable prognosis [7] and many mast cells have been associated with an adverse clinical outcome [21]. Interactions between mast cells and eosinophils in Hodgkin lymphomas are attributed to the CD30L-CD30 interaction [22].

Tumour infiltrating eosinophils have previously been investigated in colon carcinomas [6,8] but little data is known about breast cancer. In colon cancer a high amount of stromal eosinophils have correlated to a better prognosis.

In brief, all patients except one underwent surgery, mastectomy in 121 and sector resection in 112. Postoperative radiotherapy was given to 204 and adjuvant chemotherapy to 92 patients. The chemotherapy regimen was CMF (cyclophosphamide, methotrexate and 5-fluorouracil) in 83 patients or FEC (cyclophosphamide, epirubicine and 5-fluorouracil) in 6 patients and three patients had other chemotherapy regimen. Adjuvant endocrine therapy with either tamoxifen (n = 82) or toremifen (n = 20) was given to 102 patients.

Grading was done according to Elston-Ellis [27]. Sixty-five (28%) were grade 1, 98 (42%) were grade 2 and 71 (30%) were grade 3. (Table ​(Table11).

Twenty-two patients relapsed locally (localisation: chest 14 patients, axilla 5 patients and clavicular lymph nodes 3 patients). 58 patients developed distant metastasis. The median follow-up time of surviving patients was 62 months (range 17–96).

Mast cells were found mainly in the tumour stroma adjacent to the neoplastic cells (fig ​(fig1)1) but in some cases mast cells infiltrated within the islands of tumour cells.

Mean mast cell count was 7.3 (range 0–59). Eosinophils were not present at all in any tumour. Mast cells correlated significantly to low grade tumours (p = 0.001) and ER positivity (p < 0.0005). There was no correlation to the proliferation marker Ki 67. Mean mast cell count had no significant impact on metastasis-free survival (p = 0.133, relative hazard for high-versus low-mast 0.67, 95% confidence level 0.40 – 1.13) (fig ​(fig2),2), overall survival (p = 0.17, relative hazard 0.66, 95% CI 0.37–1.20) or local recurrence (p = 0.73, relative hazard 0.86, 95% CI 0.36–2.05).

The presence of mast cells was associated to low tumour grade and estrogenreceptor positivity. These are factors that are associated with a favourable prognosis in breast cancer. This might, thus be interpreted as that many mast cells is an additive favourable prognostic sign even though it was not an independent prognostic marker in this study. Eosinophils were not present at all in any of the tumour samples.

Although the mast cell count did not have a statistical impact on disease-free or overall survival in this study, this may well be due to the small number of patients. A non-significant trend towards both an improved local and distant tumour control was seen in patients with high mast cell counts, as well as an improved survival. The magnitude of this putative prognostic impact, however, seemed to be smaller than with classical clinical prognostic factors like nodal status and tumour size [28].

Mast cells accumulate around tumours and could either promote or inhibit tumour growth depending on the local stromal conditions. The presence of stromal mast cells in other malignant tumours have been of interest, but comprehensive studies are few. In colon cancer, a high amount of mast cells have been associated with lower rates of lymph node metastasis and distant metastasis [29] and many eosinophils have been associated with a better prognosis [6]. In lung cancers, a higher mast cell count has been correlated to tumour progression [30] and also correlated to microvessel density [31] in some studies, but in another study there was a lack of correlation between mast cells, eosinophils and microvessels [32]. In squamous cell carcinomas of the esophagus [33] and cervix [34] a high number of mast cells in the tumours were likewise associated to both microvessel density and tumour progression. Similarly, in malignant melanomas [35] and Hodgkin lymphomas [21] mast cells have been related to an adverse clinical outcome. The finding of many stromal mast cells close to microvessel and the association to microvessel density might be explained by contribution of mast cells to neo-angiogenesis in these tumours. However, our finding of the correlation of large number of mast cells to favourable prognostic factors in breast cancer indicate that other factors must be taken into consideration. Thus, the presence of stromal mast cells in different tumours and their precise role in the tumourigenesis needs to be further investigated in order to elucidate the different mechanisms behind.