Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77005, USA.
Mod Pathol. 2013 Sep;26(9):1153-60. doi: 10.1038/modpathol.2013.59. Epub 2013 Apr 5.
In the American Joint Committee on Cancer (AJCC)-TNM (2009) staging system, the key prognostic factor in cutaneous melanoma is the depth of dermal invasion (Breslow thickness) with further refinement according to the presence of epidermal ulceration or dermal mitoses. Immunodetection of phosphohistone H3 has been shown to facilitate the identification of mitotic figures in various neoplasms. We selected 120 cases of primary cutaneous melanoma with completely annotated histopathologic parameters and clinical outcomes and performed double immunohistochemical staining for MLANA (Mart-1/Melan-A) and phosphohistone H3. One hundred and thirteen cases were amenable to antiphosphohistone H3 staining from 66 men and 47 women, with mean age of 64 years (9-93), including 61 superficial spreading type, 24 nodular, 6 lentigo maligna, 8 acral lentiginous, and 14 unclassified. The mean Breslow thickness was 2.53 mm (0.20-25), ulceration was present in 25/113 (22%) and the mean mitotic count was 3.2/mm(2) (<1-29/mm(2)). In 27/113 (24%) of the cases, antiphosphohistone H3 failed to highlight mitotic figures anywhere in the tissue (normal or tumor cell), whereas in 86/113 (76%) antiphosphohistone H3 detected at least one mitotic figure. Among the latter, antiphosphohistone H3 did not detect mitotic figures in dermal tumor cells in 37/86 cases (43%), whereas anti-PHH3 identified at least one melanocytic mitotic figure in the other 49/86 cases (57%; range: 1-66/mm(2)). The relationship between phosphohistone H3 and manual mitotic count was statistically significant (Pearson correlation=0.59, P<0.0001). Logistic regression analyses demonstrated an association between the development of subsequent metastatic disease and the following variables: mitotic figures (odds ratio (OR)=5.7; P=0.0001); phosphohistone H3-positive mitotic figures (OR=3.0; P=0.008); Breslow thickness (OR=4.0 per mm; P=0.0002); ulceration (OR=3.94; P=0.008). The application of phosphohistone H3 immunohistochemistry to the description of primary cutaneous melanoma is useful in identifying mitotic figures, improves upon the specificity of this designation when used together with MLANA, and correlates with an increased risk for metastasis in univariate analyses.
在 AJCC-TNM（2009）分期系统中，皮肤黑色素瘤的关键预后因素是真皮浸润深度（Breslow 厚度），并根据表皮溃疡或真皮有丝分裂的存在进行进一步细化。磷酸组蛋白 H3 的免疫检测已被证明有助于在各种肿瘤中识别有丝分裂图。我们选择了 120 例具有完全注释的组织病理学参数和临床结果的原发性皮肤黑色素瘤，并对 MLANA（Mart-1/Melan-A）和磷酸组蛋白 H3 进行了双重免疫组织化学染色。在 66 名男性和 47 名女性中，有 113 例可进行抗磷酸组蛋白 H3 染色，平均年龄为 64 岁（9-93），包括 61 例浅表扩散型、24 例结节型、6 例恶性雀斑样痣、8 例肢端雀斑样痣和 14 例未分类。平均 Breslow 厚度为 2.53mm（0.20-25），25/113（22%）存在溃疡，平均有丝分裂计数为 3.2/mm2（<1-29/mm2）。在 113 例中的 27 例（24%）中，抗磷酸组蛋白 H3 未能在组织的任何部位突出有丝分裂图（正常或肿瘤细胞），而在 86/113（76%）例中，抗磷酸组蛋白 H3 检测到至少一个有丝分裂图。在后一组中，抗磷酸组蛋白 H3 在 37/86 例（43%）中未检测到真皮肿瘤细胞中的有丝分裂图，而在其他 49/86 例（57%；范围：1-66/mm2）中，抗-PHH3 至少检测到一个黑素细胞有丝分裂图。磷酸组蛋白 H3 与手动有丝分裂计数之间的关系具有统计学意义（Pearson 相关系数=0.59，P<0.0001）。逻辑回归分析显示，随后发生转移性疾病与以下变量有关：有丝分裂数（优势比（OR）=5.7；P=0.0001）；磷酸组蛋白 H3 阳性有丝分裂数（OR=3.0；P=0.008）；Breslow 厚度（OR=4.0/mm；P=0.0002）；溃疡（OR=3.94；P=0.008）。磷酸组蛋白 H3 免疫组织化学在原发性皮肤黑色素瘤的描述中的应用有助于识别有丝分裂图，当与 MLANA 一起使用时提高了这一指定的特异性，并在单变量分析中与转移风险增加相关。
