COX‐2 expression in lobular <i>in situ</i> neoplasia of the breast: correlation with histopathological grading system according to the Tavassoli classification

Perrone, Giuseppe; Zagami, Mariagiovanna; Santini, Daniele; Vincenzi, Bruno; Gullotta, G; Morini, Sergio; Battista, C.; Guerriero, Gabriella; Altomare, Vittorio; Tonini, Giuseppe; Rabitti, Carla

doi:10.1111/j.1365-2559.2007.02731.x

Cited by 11 publications

(12 citation statements)

References 29 publications

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“…The evaluation of COX-2 expression in different LIN grades showed very similar results to those in our previous analysis performed on another LIN lesion series [25]. A significant correlation was found between COX-2 and LIN grade (r=−0.394; p=0.013).…”

Section: Correlations Between Immunohistochemical and Patients' Charasupporting

confidence: 84%

“…Macrophages, used as positive internal control, showed only a cytoplasm staining pattern coherently with our recent publications [24,25]. Membrane COX-2 expression was found in 29 (74.4%) cases, while only 13 (33.3%) lesions showed a cytoplasmic positivity.…”

Section: Immunohistochemical Stainingsupporting

confidence: 72%

“…Subsequently, we have demonstrated that COX-2 is also expressed in human LIN of the breast. Moreover, when LIN lesions were stratified following Tavassoli classification [32], a significant statistical difference was found between LIN3 vs LIN1-2, thus let hypothesize that this different protein expression pattern could reflect a different biological behavior [25]. Our results have also demonstrated that COX-2 immunostaining in LIN lesions, differently from what was previously established in ductal intraepithelial lesions [24], shows a prevalent membrane pattern, suggesting that COX-2 protein is mainly located in plasma membrane of LIN cells.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, our results have demonstrated that COX-2 immunostaining in lobular intraepithelial neoplasia (LIN) shows a prevalent membrane pattern [25] suggesting that COX-2 protein is mainly located in plasma membrane of LIN lesion cells.…”

Section: Introductionmentioning

confidence: 86%

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COX-2 localization within plasma membrane caveolae-like structures in human lobular intraepithelial neoplasia of the breast

et al. 2007

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Cyclooxygenase-2 (COX-2) is highly expressed in human intraepithelial neoplasia of the breast and takes part in the molecular pathway implicated in progression of breast cancer. Recently, we demonstrated that COX-2 protein is mainly located in plasma membrane of lobular intraepithelial neoplasia (LIN) cells suggesting a localization in caveolae-like structures. The aim of the present study is to establish subcellular locations of COX-2 and its colocalization with caveolin-1 (CAV-1) to caveolae structures in LIN. To establish a relationship between COX-2 and CAV-1, 39 LINs were studied by immunohistochemistry and confocal microscopy analysis. COX-2 and CAV-1 expression was observed respectively in 79.5 and in 94.9% of LIN studied. A positive correlation was found between membrane COX-2 staining pattern and CAV-1 expression, while no correlation was found between cytoplasm COX-2 staining pattern and CAV-1. Confocal analysis showed that COX-2 localized to plasma membrane was strictly associated to CAV-1 suggesting that an amount of COX-2 protein is placed in caveolae-like structures. Our results show that COX-2 is localized within caveolae compartment and colocalized with CAV-1 protein in LIN lesions. Because caveolae are rich in signaling molecules, this COX-2 compartment may play an important role in diverse breast cancer carcinogenesis processes.

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Section: Correlations Between Immunohistochemical and Patients' Charasupporting

confidence: 84%

Section: Immunohistochemical Stainingsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 86%

See 2 more Smart Citations

COX-2 localization within plasma membrane caveolae-like structures in human lobular intraepithelial neoplasia of the breast

et al. 2007

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“…In a recent report, evaluating expression of Cox-2, an enzymatic protein linked to the development of breast cancer, similar results were presented. 33 Take together, a provocative possible explanation is that lobular intraepithelial neoplasia grade 3, rather than grades 1 and 2 lesions, is a precursor lesion of invasive lobular carcinoma rather than a simple risk factor. In summary, data presented here confirm and extend the in vitro findings of others and show for the first time that Cav-1 may have a key role as a tumour suppressor in the lobular breast carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Caveolin-1 expression in human breast lobular cancer progression

et al. 2009

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Caveolin-1 is the principal structural protein of caveolae, and caveolin-1 gene plays a role as a tumour suppressor gene in human mammary cancer-derived cells. However, limited data are available concerning caveolin-1 expression in human breast cancer tissue. We evaluated caveolin-1 expression in normal lobular epithelial cells and in the whole human lobular neoplasia spectrum disease, with the aim to examine differences of caveolin-1 expression in human lobular neoplasia progression. We selected 147 cases of pure lobular lesions, ie lobular intraepithelial neoplasia and invasive lobular carcinoma, from 112 patients. Presence of caveolin-1 was evaluated by immunohistochemistry. Among 81 lobular intraepithelial neoplasia lesions studied, 43% were associated with invasive lobular carcinoma, with positive correlation between lobular intraepithelial neoplasia grade and presence of invasive component (P ¼ 0.01). In total, 64% of lobular lesions were positive for caveolin-1 (81% lobular intraepithelial neoplasia and 42% invasive lobular carcinoma), and a significant difference in terms of caveolin-1 expression was present between lobular intraepithelial neoplasia and invasive lobular carcinoma (P ¼ 0.0001). Variations in caveolin-1 expression were evident among the different lobular intraepithelial neoplasia grades (91% grade 1, 68% grade 2, 35% grade 3); the difference was significant comparing lobular intraepithelial neoplasia grade 3 vs 1 (P ¼ 0.0001) and grade 3 vs 2 (P ¼ 0.007) but not grade 1 vs 2. Furthermore, significant differences were found between lobular intraepithelial neoplasia grades 1 and 2 vs invasive lobular carcinoma (P ¼ 0.0001), but not between lobular intraepithelial neoplasia grade 3 and invasive lobular carcinoma (P ¼ 0.196). In conclusion, variations of caveolin-1 expression may have an important role in the progression of human breast lobular cancer; in addition, they confirm the powerful clinical impact of the lobular intraepithelial neoplasia classification for lobular intraepithelial neoplasia, supporting the direct origin of invasive lobular carcinoma from clonal expansion of the lobular intraepithelial neoplasia lesions cells.

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Intraepithelial neoplasia of the breast

Wang

2009

Intraepithelial Neoplasia

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COX‐2 expression in lobular in situ neoplasia of the breast: correlation with histopathological grading system according to the Tavassoli classification

Abstract: COX-2 is highly expressed in LIN, supporting a role for this protein in the early stage of breast carcinogenesis, representing the rationale for using COX-2 selective inhibitors in the earliest stages of breast cancer.

Cited by 11 publications

References 29 publications

COX-2 localization within plasma membrane caveolae-like structures in human lobular intraepithelial neoplasia of the breast

COX-2 localization within plasma membrane caveolae-like structures in human lobular intraepithelial neoplasia of the breast

Caveolin-1 expression in human breast lobular cancer progression

Intraepithelial neoplasia of the breast

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