Kleer C G, Giordano T J, Braun T, Oberman H A
Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109-0054, USA.
Mod Pathol. 2001 Mar;14(3):185-90. doi: 10.1038/modpathol.3880282.
The histologic distinction between benign and malignant Phyllodes tumors (PT) is often difficult and arbitrary. We analyzed a group of benign and malignant PT to determine whether specific histologic features and expression of Ki-67 and p53 could be useful in distinguishing benign PT from malignant tumors. We also determined whether deletions in Chromosome 3p at the FHIT and hMLH1 loci are common abnormalities in PT. Twenty PT were histologically classified as benign (7) or malignant (13). Seven of the malignant PT were low grade, and six were high grade. Ki-67 and p53 immunohistochemistry was performed on all tumors and analyzed for the stromal and for the epithelial component. PCR-based loss of heterozygosity analyses were performed with the following markers on Chromosome 3p: D3S1478 (3p21.2--21.3), D3S1289 (3p21.1--21.2), and D3S1295 (3p14.3--21.1). The distribution of immunoreactivity for Ki-67 was analyzed by quantifying the percentage of positive nuclei and expressed as the labeling index (LI). Patients' ages ranged from 13 to 71 years (median: 51 y). After a mean follow-up period of 8 years, none of the PT metastasized, whereas three recurred locally. Although malignant PT were larger than benign PT (means, 7.1 versus 4.3 cm), this difference was not statistically significant. Five tumors had infiltrating margins, and 14 were circumscribed. The Ki-67 LI in low-grade malignant PT (16 +/- 25.5) was significantly higher than that in benign PT (3.6 +/- 4.8), whereas the LI in the high-grade malignant PT group (50 +/- 21.9) was significantly higher than that in low-grade malignant tumors (P =.012). The Ki-67 LI in the three tumors that recurred was less than 10%. Two of seven (29%) benign PT were focally positive for p53, whereas four of seven (57%) low-grade malignant and three of six (50%) high-grade malignant PT were diffusely positive for p53. The three tumors that recurred initially were histologically benign, as were two of the recurrences. One recurrent tumor evolved to a high-grade malignant PT. Margins were greater than 1 cm in all tumors except four, three of which recurred locally. No allelic loss of 3p was found. In summary, Ki-67 expression may assist in distinguishing benign from malignant PT in diagnostically difficult cases. 3p deletions do not play a significant role in the development of these tumors. Neither Ki-67 nor p53 can reliably predict recurrence. Histologically high-grade malignant PT have a favorable prognosis if widely excised. We emphasize the importance of adequate margins in the treatment of benign and malignant PT.
乳腺叶状肿瘤（PT）的良恶性在组织学上的区分往往困难且具有主观性。我们分析了一组良性和恶性PT，以确定特定的组织学特征以及Ki-67和p53的表达是否有助于区分良性PT与恶性肿瘤。我们还确定了在FHIT和hMLH1基因座处的3号染色体短臂缺失是否是PT中的常见异常。20例PT在组织学上被分类为良性（7例）或恶性（13例）。其中7例恶性PT为低级别，6例为高级别。对所有肿瘤进行了Ki-67和p53免疫组织化学检测，并分别分析了间质成分和上皮成分。使用位于3号染色体短臂上的以下标记进行基于聚合酶链反应（PCR）的杂合性缺失分析：D3S1478（3p21.2 - 21.3）、D3S1289（3p21.1 - 21.2）和D3S1295（3p14.3 - 21.1）。通过量化阳性细胞核的百分比来分析Ki-67的免疫反应性分布，并将其表示为标记指数（LI）。患者年龄范围为13至71岁（中位数：51岁）。经过平均8年的随访期，没有PT发生转移，而有3例出现局部复发。虽然恶性PT比良性PT更大（平均值分别为7.1 cm和4.3 cm），但这种差异无统计学意义。5个肿瘤有浸润性边缘，14个为边界清楚。低级别恶性PT的Ki-67 LI（16 ± 25.5）显著高于良性PT（3.6 ± 4.8），而高级别恶性PT组的LI（50 ± 21.9）显著高于低级别恶性肿瘤（P = 0.012）。3例复发肿瘤的Ki-67 LI小于10%。7例良性PT中有2例（29%）p53呈局灶性阳性，而7例低级别恶性PT中有4例（57%）、6例高级别恶性PT中有3例（50%）p53呈弥漫性阳性。最初复发的3个肿瘤在组织学上为良性，复发的肿瘤中有2个也是如此。1个复发肿瘤演变为高级别恶性PT。除4个肿瘤外，所有肿瘤的边缘均大于1 cm，其中3个局部复发。未发现3号染色体短臂的等位基因缺失。总之，在诊断困难的病例中Ki-67表达可能有助于区分良性与恶性PT。3号染色体短臂缺失在这些肿瘤的发生发展中不发挥重要作用。Ki-67和p53均不能可靠地预测复发。组织学上高级别恶性PT如果广泛切除则预后良好。我们强调在良性和恶性PT治疗中足够手术切缘的重要性。
