天冬氨酰內(nèi)肽酶又稱天冬酰胺肽鏈內(nèi)切酶,、半胱氨酸蛋白酶、血紅蛋白酶,、豆莢蛋白酶,，屬于蛋白質(zhì)水解酶，其編碼基因?yàn)長GMN,，對乳腺浸潤癌的細(xì)胞增殖具有調(diào)節(jié)作用,。不過，其對乳腺導(dǎo)管原位癌的作用尚不明確,。

　　2018年11月14日,，美國和加拿大病理學(xué)會、英國《自然》旗下《現(xiàn)代病理學(xué)》在線發(fā)表英國諾丁漢大學(xué),、澳大利亞墨爾本大學(xué),、彼得麥卡倫癌癥中心、加拿大麥吉爾大學(xué),、埃及阿斯尤特大學(xué),、米努夫大學(xué)、伊拉克穆斯坦西里亞大學(xué)的研究報(bào)告,，分析了乳腺導(dǎo)管原位癌的天冬氨酰內(nèi)肽酶蛋白質(zhì)表達(dá)水平,，并且對其預(yù)后意義進(jìn)行了評估。

　　該研究通過組織微陣列（組織芯片）對1015例乳腺導(dǎo)管原位癌患者（單純型乳腺導(dǎo)管原位癌776例,、乳腺浸潤癌混合型乳腺導(dǎo)管原位癌239例）的天冬氨酰內(nèi)肽酶進(jìn)行免疫組織化學(xué)評定,，對腫瘤細(xì)胞以及周圍基質(zhì)的天冬氨酰內(nèi)肽酶免疫反應(yīng)活性進(jìn)行評分,，并與臨床病理學(xué)指標(biāo)和患者結(jié)局進(jìn)行關(guān)聯(lián)。

　　結(jié)果發(fā)現(xiàn),，23%的單純型乳腺導(dǎo)管原位癌可見天冬氨酰內(nèi)肽酶高表達(dá),，并且與高風(fēng)險(xiǎn)乳腺導(dǎo)管原位癌的特征相關(guān)，包括腫瘤細(xì)胞核分級較高,、粉刺樣壞死,、激素受體陰性、HER2陽性,、增殖指數(shù)較高,。混合型乳腺導(dǎo)管原位癌與單純型乳腺導(dǎo)管原位癌相比，天冬氨酰內(nèi)肽酶表達(dá)水平顯著較高（P<0.0001）,。對于混合型乳腺導(dǎo)管原位癌,，浸潤癌成分與原位癌成分相比，天冬氨酰內(nèi)肽酶表達(dá)水平顯著較高（P<0.0001）,。天冬氨酰內(nèi)肽酶可以獨(dú)立預(yù)測局部復(fù)發(fā)時間較短（P=0.0003）,、局部浸潤復(fù)發(fā)時間較短（P=0.002）。當(dāng)結(jié)合其他風(fēng)險(xiǎn)因素時,，天冬氨酰內(nèi)肽酶可以更好地對患者進(jìn)行風(fēng)險(xiǎn)分層,。

　　因此，該研究結(jié)果表明,，天冬氨酰內(nèi)肽酶高表達(dá)與乳腺導(dǎo)管原位癌預(yù)后不良相關(guān),，可能成為預(yù)測乳腺導(dǎo)管原位癌進(jìn)展為浸潤癌的潛在標(biāo)志。

Mod Pathol. 2018 Nov 14. [Epub ahead of print]

Legumain is an independent predictor for invasive recurrence in breast ductal carcinoma in situ.

Michael S. Toss, Islam M Miligy, Kylie L. Gorringe, L. McCaffrey, Abdulbaqi AlKawaz, Asima Abidi, Ian O. Ellis, Andrew R. Green, Emad A. Rakha.

The University of Nottingham, Nottingham University Hospital NHS Trust, Nottingham City Hospital, Nottingham, UK; Assiut University, Assiut, Egypt; Menoufia University, Shebeen El-Kom, Egypt; Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; University of Melbourne, Parkville, VIC, Australia; McGill University, Montreal, QC, Canada; Al Mustansiriya University, Baghdad, Iraq.

Legumain is a proteolytic enzyme that plays a role in the regulation of cell proliferation in invasive breast cancer. Studies evaluating its role in ductal carcinoma in situ (DCIS) are lacking. Here, we aimed to characterize legumain protein expression in DCIS and evaluate its prognostic significance. Legumain was assessed immunohistochemically in a tissue microarray of a well-characterized cohort of DCIS (n = 776 pure DCIS and n = 239 DCIS associated with invasive breast cancer (DCIS-mixed)). Legumain immunoreactivity was scored in tumor cells and surrounding stroma and related to clinicopathological parameters and patient outcome. High legumain expression was observed in 23% of pure DCIS and was associated with features of high-risk DCIS including higher nuclear grade, comedo necrosis, hormone receptor negativity, HER2 positivity, and higher proliferation index. Legumain expression was higher in DCIS associated with invasive breast cancer than in pure DCIS (p < 0.0001). In the DCIS-mixed cohort, the invasive component showed higher legumain expression than the DCIS component (p < 0.0001). Legumain was an independent predictor of shorter local recurrencefree interval for all recurrences (p = 0.0003) and for invasive recurrences (p = 0.002). When incorporated with other risk factors, legumain provided better patient risk stratification. High legumain expression is associated with poor prognosis in DCIS and could be a potential marker to predict DCIS progression to invasive disease.

DOI: 10.1038/s41379-018-0180-x