Kurbel Sven, Marjanović Ksenija, Dmitrović Branko
Department of Physiology, Osijek Medical Faculty, Osijek, Croatia.
Theor Biol Med Model. 2014 Jun 11;11:29. doi: 10.1186/1742-4682-11-29.
A previous theoretic model (Tumour Biol 2013;34:1-7.) that breast tumor types differ in the relative rate of tissue invasion was elaborated and developed on a consecutive case series.
Histologic data of 68 ductal breast cancer in situ (DCIS) and 1180 invasive ductal cancer (IDC) patients were collected and analyzed.
ER+PgR- phenotype was more common in Luminal B2 than among the pooled Luminal A&B1 (p = 0.0002), and more frequent in Luminal B1 than in Luminal A (p = 0.0167). The same phenotype was associated with the age older than 54 years in Luminal B1 and in B2 patients. HER2 type cancers were more frequent in older patients (p = 0.0038).Tumor progression from DCIS to IDC was found 39% faster than the average in Luminal B1 tumors, supporting the clinical importance of this tumor type. A rare combination of low Ki-67 in HER2 type cancers (only 14% of HER2 type cancers) showed very slow transition to IDC (occurring at only 53.55% of average progression rate), while triple-negative cancers progressed faster than the average, despite Ki-67 value (104.63% for low and 114.27% for high Ki-67 tumors).In three tumor types with positive steroid receptors the ER+PgR- phenotype showed slower IDC transition than the ER+PgR+ phenotype of the same tumor type (difference in progression rate was 38% for Luminal A, 46% for Luminal B1 and 67% for Luminal B2 with Ki67 > 14%).Triple-negative tumors in younger patients exceeded the expected average progression rate by 24%, while in HER2 type tumors, the rate of tissue invasion was in younger patients 20% lower than the expected value.
The relative rate of tissue invasion differed substantialy among our patients. Differences depended on tumor types, steroid expression phenotypes and age. The dysfunctional ERs in the ER+PgR- phenotype showed slower rates of tissue invasion, suggesting that ligand binding to functional breast tumor ERs, beside promoting the PgR expression, possibly also promotes tumor transition to the invasive phase.In triple-negative tumors, an age dependent premenopausal mechanism possibly acted as an accelerator of tissue invasion, while faster tissue invasion by HER2-overexpressed tumors in older patients possibly depended on an unidentified mechanism that takes more time to be acquired, so it was less present in premenopausal patients.
之前的一个理论模型（《肿瘤生物学》2013年；34:1 - 7）阐述并发展了乳腺肿瘤类型在组织侵袭相对速率上存在差异的观点，该模型基于一个连续病例系列构建。
收集并分析了68例乳腺导管原位癌（DCIS）和1180例浸润性导管癌（IDC）患者的组织学数据。
ER + PgR - 表型在Luminal B2型中比在合并的Luminal A&B1型中更常见（p = 0.0002），在Luminal B1型中比在Luminal A型中更频繁（p = 0.0167）。相同表型在Luminal B1型和B2型患者中与年龄大于54岁相关。HER2型癌症在老年患者中更常见（p = 0.0038）。发现Luminal B1型肿瘤从DCIS进展为IDC的速度比平均速度快39%，支持了这种肿瘤类型的临床重要性。HER2型癌症中低Ki - 67的罕见组合（仅占HER2型癌症的14%）向IDC的转变非常缓慢（仅以平均进展速度的53.55%发生），而三阴性癌症进展速度比平均速度快，尽管有Ki - 67值（低Ki - 67肿瘤为104.63%，高Ki - 67肿瘤为114.27%）。在三种具有阳性类固醇受体的肿瘤类型中，ER + PgR - 表型向IDC的转变比同一肿瘤类型的ER + PgR + 表型慢（对于Luminal A，进展速度差异为38%；对于Luminal B1，为46%；对于Luminal B2，Ki67＞14%时为67%）。年轻患者中的三阴性肿瘤超过预期平均进展速度24%，而在HER2型肿瘤中，年轻患者的组织侵袭率比预期值低20%。
我们的患者中组织侵袭的相对速率存在显著差异。差异取决于肿瘤类型、类固醇表达表型和年龄。ER + PgR - 表型中功能失调的雌激素受体显示出较慢的组织侵袭速率，这表明配体与功能性乳腺肿瘤雌激素受体结合，除了促进PgR表达外，可能还促进肿瘤向侵袭期的转变。在三阴性肿瘤中，一种年龄依赖性的绝经前机制可能充当组织侵袭的加速器，而老年患者中HER2过表达肿瘤更快的组织侵袭可能取决于一种尚未明确的机制，这种机制需要更多时间来获得，因此在绝经前患者中较少出现。
