Expression of aromatase and estrogen sulfotransferase in preinvasive and invasive breast cancer

Hudelist, Gernot; Wülfing, P.; Kersting, Christian; Bürger, Horst; Mattsson, B; Czerwenka, K.; Kubista, E.; Gschwantler‐Kaulich, Daphne; Fink-Retter, A.; Singer, Christian F.

doi:10.1007/s00432-007-0249-2

Cited by 21 publications

(19 citation statements)

References 22 publications

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“…In relation to the nuclear grade our results are similar to those found by Hudelist et al (2008) 12 ,who evaluated 96 samples of DCIS, and 104 samples of DCIS and IDC in the same samples. They found that in DCIS there was no statistically significant difference in aromatase expression between high, moderate and low grade tumors.…”

Section: Discussionsupporting

confidence: 89%

“…It is found in women of reproductive age and also in post-menopausal 1,3 . The great difference between these two phases of life is that in postmenopausal women extra-ovarian aromatase plays a fundamental role in the estrogen synthesis (7,12) . The peripheral conversion of androgens to estrogens occurs in the adipose tissue, muscle, skin and also in the breast tissue itself and especially in the latter, significant enhancement of conversion due to higher levels of aromatase expression is associated with malignant changes 10,35,36 .…”

Section: Discussionmentioning

confidence: 99%

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The interaction between aromatase, metalloproteinase 2,9 and cd44 in breast cancer

Bagnoli

Oliveira²,

Silva

et al. 2010

Rev. Assoc. Med. Bras.

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SummaryobjectIve. This study intends to verify the expression levels and correlation of aromatase, matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9) and CD44 in ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) when both are found in the same breast. Methods. One hundred and ten cases were evaluated by tissue microarray (TMA) and immunohistochemically screened with anti-aromatase polyclonal antibodies, anti-MMP-2 monoclonal antibodies, anti-MMP-9 policlonal antibodies and anti-CD44 monoclonal antibodies. results. Aromatase was expressed in IDC and DCIS in 63 (57.3%) and 60 (67%) of the cases respectively; MMP-2 was similarly expressed in IDC and DCIS in 15 (13.60%) cases; MMP-9 was positively expressed in IDC and DCIS in 83 (75.50%) and 82 (74.50%) cases, respectively; CD44 was positively expressed in IDC and DCIS in 49 (44.50%) and 48 (42.60%) of the cases, respectively; all of them were highly correlated (p<0,001). The correlation analysis found positive, statistically significant correlation, in IDC between aromatase and MMP-2 (p<0.001) and between aromatase and MMP-9 (p=0.034). Positive correlation between aromatase and MMP-2 (p<0.001) and between MMP-9 and CD44 (p=0.030) were found in DCIS. conclusIon. These results allow us to conclude that aromatase through local estrogen synthesis in breast tissue plays an important role in breast carcinogenesis, mainly influencing MMP-2 and MMP-9 which are important participants in tumor cell invasion and dependence of their connection to CD44 for action.Key words: Aromatase. Matrix metalloproteinase 2. Matrix metalloproteinase 9. Antigens CD44. Carcinoma ductal breast.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

The interaction between aromatase, metalloproteinase 2,9 and cd44 in breast cancer

Bagnoli

Oliveira²,

Silva

et al. 2010

Rev. Assoc. Med. Bras.

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“…The results show that estrogen synthesis should be more expressive in tissues adjacent to the tumor, modulating tumor growth through paracrine, autocrine and intracrine mechanisms. 15,16 Though we found a trend towards greater aromatase expression in cases of nuclear grade III DCIS with comedonecrosis, the data were not statistically significant and similar to other findings described in the literature. 7 Greater aromatase expression has been been found in cases of nuclear grade III IDCs (p = 0.03), 4 similar to what we found in analyzing IDCs (p = 0.05).…”

Section: Discussionsupporting

confidence: 74%

Expressão da aromatase em carcinomas de mama ductais invasivo e in situ presentes na mesma mama

Oliveira¹,

Ribeiro²,

Rossi³

et al. 2009

Rev. Assoc. Med. Bras.

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Objective. To evaluate aromatase enzyme expression in invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) present in the same breast in adjacent epithelium and stroma. Methods. Forty-five surgical samples were collected from mastectomies and quadrantectomies from patients with simultaneous stage I and II IDC and DCIS. Aromatase enzyme expression analysis used anti-aromatase polyclonal antibodies. The samples were classified by number and intensity of stained cells. Results. Aromatase expression was positive in 32 (71%) IDC cases and negative in 13 (29%). The same results were obtained in the DCIS, showing a perfect positive correlation. In normal epithelium, aromatase expression was positive in 19 (42.2%) and negative in 26 (57.8%) cases, a statistically significant positive correlation when compared to IDC and DCIS (p < 0.01). Analysis of normal stroma revealed only 7 (15.5%) of the 45 cases of positive expression, showing no correlation with any variables analyzed for aromatase expression. As for tumor stroma, aromatase expression was positive in 36 (80%) and negative in 9 (20%) of cases, a statistically significant correlation with IDC (p < 0.01) and DCIS (p < 0.01) expression. No statistically significant differences were found by comparing aromatase expression results in IDC, DCIS, normal epithelium and tumor stroma with nuclear grade, histological grade, tumor size and age. cOnclusiOn. Results showed high levels of correlation between aromatase expression in IDC, DCIS, normal epithelium and tumor stroma, suggesting the enzyme has a possible autocrine and paracrine mechanism in breast cancer.

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“…While the presence of such enzymes in the primary tumor has been demonstrated previously, considerably less is known about such a network in corresponding lymph nodes [13]. This is somewhat surprising since tumor cells have been shown to lose estrogen responsiveness as they progress and develop distant metastases.…”

Section: Discussionmentioning

confidence: 91%

“…Suzuki et al [32] found a significant inverse correlation of EST with tumor size and lymph node status, and a positive correlation with a decreased risk of recurrence. Hudelist et al [13] investigated the differential expression of EST in preinvasive and invasive breast cancer and found a significant downregulation in high-grade DCIS compared to non-high-grade cases. To date, sulfotransferase expression in lymphatic metastases has never been investigated.…”

Section: Discussionmentioning

confidence: 98%

Differential expression pattern of estrogen receptors, aromatase, and sulfotransferase in breast cancer tissue and corresponding lymph node metastases

et al. 2010

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Patients with hormone receptor positive breast cancer who are treated with endocrine therapy generally have a good prognosis. However, resistance to hormonal therapy and progression occurs, and the reasons for this are manifold. It has been proposed that the local estrogenic environment has a role in the process of local invasion and progression. We have determined the expression pattern of estrogen receptor α, estrogen receptor β, and the epithelial and stromal expression of the estrogen-metabolizing enzymes aromatase and sulfotransferase by immunohistochemistry in tissue arrays, containing 50 paraffin-embedded sets of tissues obtained from breast cancer and from corresponding metastatic axillary lymph nodes of the same patients. We have found statistically significant higher estrogen receptors α and β expression in primary tumors than in corresponding lymph node metastases (p = 0.0004 and p = 0.003, respectively). Aromatase was also expressed more frequently in epithelial as well as in stromal cells of the malignant tumor when compared to according lymph node metastases (p = 0.08 and p = 0.12, respectively). While in lymph node metastases only estrogen receptor α and stromal aromatase expression were correlated (p = 0.01), significant associations were seen between the estrogen receptor β and sromal aromatase, and epithelial sulfotransferase (p = 0.0006 and p = 0.03, respectively) in the primary tumor. We hypothesize that the decreased expression of local estrogens by aromatase, in combination with a decreased expression of estrogen receptors α and β in lymphatic metastases, renders these metastases hormone insensitive and could contribute to the poor response to endocrine therapy that is often seen in nodal-positive tumors.

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Expression of aromatase and estrogen sulfotransferase in preinvasive and invasive breast cancer

Cited by 21 publications

References 22 publications

The interaction between aromatase, metalloproteinase 2,9 and cd44 in breast cancer

The interaction between aromatase, metalloproteinase 2,9 and cd44 in breast cancer

Expressão da aromatase em carcinomas de mama ductais invasivo e in situ presentes na mesma mama

Differential expression pattern of estrogen receptors, aromatase, and sulfotransferase in breast cancer tissue and corresponding lymph node metastases

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