Brower S T, Ahmed S, Tartter P I, Bleiweiss I, Amberson J B
Department of Surgery, Mount Sinai Medical Center, New York, New York 10029, USA.
Ann Surg Oncol. 1995 Sep;2(5):440-4. doi: 10.1007/BF02306378.
Many invasive breast cancers are accompanied by a variety of noninvasive components. Histological distinctions have been made between these components, but to understand their importance, it is essential to examine their molecular biology.
Proliferative indices, oncoproteins, and steroid receptor expression were compared for invasive breast cancers containing comedo-type ductal carcinoma in situ (n = 35), noncomedo-type ductal carcinoma in situ (n = 34), and pure invasive cancers (n = 49). Ploidy, S-phase fraction, Ki-67 staining, estrogen receptor (ER), progesterone receptor (PR), and the expression of HER-2/neu and epidermal growth factor receptor (EGFR) were evaluated in these tumors.
The comedo-invasive subgroup differed significantly from the noncomedo-invasive subgroup, demonstrating significantly higher mean ploidy (1.6 vs. 1.3; p = 0.0156), S-phase fraction (7.9% vs. 4.3%; p = 0.0066), Ki-67 staining (20.3% vs. 12.0%; p = 0.0058), and HER-2/neu values (2,247 fm/mg vs. 1,014 fm/mg; p = 0.0412) and lower ER (76 fm/mg vs. 339 fm/mg; p = 0.006) and PR values (99 fm/mg vs. 265 fm/mg; p = 0.0608). A higher percentage of comedo-invasive carcinomas demonstrated aneuploidy 71%; p = 0.0158), elevated levels of S-phase fraction (75%; p = 0.0016) and Ki-67 staining (55%; p = 0.0512), overexpression of HER-2/neu oncogene (47%; p = 0.0011), and were ER negative (35%; p = 0.0148), PR negative (47%; p = 0.0073) when compared to noncomedo-invasive carcinomas. Comedo-invasive and noncomedo-invasive tumors were comparable for nodal status and tumor size, but differences were noted for tumor differentiation and percentage of tumors that were > 1 cm. Comedo-invasive tumors were predominantly poorly differentiated (60 vs. 32%) and were > 1 cm (94 vs. 77%, p < 0.05).
Comedo-invasive cancers were comparable to pure invasive cancers for ploidy, S-phase fraction, Ki-67 staining, and ER, PR, and EGFR expression. However, comedo-invasive carcinomas had greater HER-2/neu overexpression when compared to pure invasive tumors (47 vs. 19%; p = 0.0359).
These results are consistent with the hypothesis that comedo carcinoma is a more aggressive type of ductal carcinoma in situ and may have independent prognostic value when seen in association with infiltrating ductal carcinoma. In invasive tumors, comedo carcinomas are associated with poor prognostic factors, including higher ploidy, S-phase fractions, Ki-67 staining, negative ER and PR status, poorer differentiation, larger tumors, and presence of HER-2/neu oncogene overexpression.
许多浸润性乳腺癌伴有多种非浸润性成分。已对这些成分进行了组织学区分，但要了解它们的重要性，研究其分子生物学至关重要。
比较了含有粉刺型导管原位癌（n = 35）、非粉刺型导管原位癌（n = 34）和纯浸润性癌（n = 49）的浸润性乳腺癌的增殖指数、癌蛋白和类固醇受体表达。评估了这些肿瘤的倍体、S期分数、Ki-67染色、雌激素受体（ER）、孕激素受体（PR）以及HER-2/neu和表皮生长因子受体（EGFR）的表达。
粉刺型浸润亚组与非粉刺型浸润亚组有显著差异，显示出显著更高的平均倍体（1.6对1.3；p = 0.0156）、S期分数（7.9%对4.3%；p = 0.0066）、Ki-67染色（20.3%对12.0%；p = 0.0058）以及HER-2/neu值（2247 fm/mg对1014 fm/mg；p = 0.0412），而ER（76 fm/mg对339 fm/mg；p = 0.006）和PR值（99 fm/mg对265 fm/mg；p = 0.0608）较低。与非粉刺型浸润性癌相比，更高比例的粉刺型浸润性癌表现为非整倍体（71%；p = 0.0158）、S期分数升高（75%；p = 0.0016）和Ki-67染色升高（55%；p = 0.0512）、HER-2/neu癌基因过表达（47%；p = 0.0011），且ER阴性（35%；p = 0.0148）、PR阴性（47%；p = 0.0073）。粉刺型浸润性和非粉刺型浸润性肿瘤在淋巴结状态和肿瘤大小方面具有可比性，但在肿瘤分化和肿瘤>1 cm的比例方面存在差异。粉刺型浸润性肿瘤主要为低分化（60%对32%）且>1 cm（94%对77%，p < 0.05）。
粉刺型浸润性癌在倍体、S期分数、Ki-67染色以及ER、PR和EGFR表达方面与纯浸润性癌具有可比性。然而，与纯浸润性肿瘤相比，粉刺型浸润性癌有更高的HER-2/neu过表达（47%对19%；p = 0.0359）。
这些结果与粉刺癌是一种更具侵袭性的导管原位癌类型这一假设一致，并且当与浸润性导管癌同时出现时可能具有独立的预后价值。在浸润性肿瘤中，粉刺癌与不良预后因素相关，包括更高的倍体、S期分数、Ki-67染色、ER和PR阴性状态、较差的分化、更大的肿瘤以及HER-2/neu癌基因过表达的存在。
