Guillaud Martial, Cox Dennis, Adler-Storthz Karen, Malpica Anais, Staerkel Gregg, Matisic Jasenka, Van Niekerk Dirk, Poulin Neal, Follen Michele, MacAulay Calum
Department of Cancer Imaging, British Columbia Cancer Agency, Vancouver, British Columbia.
Cytometry A. 2004 Jul;60(1):81-9. doi: 10.1002/cyto.a.20034.
As part of a project to evaluate emerging optical technologies for cervical neoplasia, our group is performing quantitative histopathological analyses of biopsy specimens from 1,190 patients. Objectives in the interim analysis are (a) quantitatively assessing progression of the neoplastic process of cervical intraepithelial neoplasia (CIN)/squamous intraepithelial lesions (SIL), (b) detecting malignancy-associated changes (MACs), and (c) phenotypically measuring human papillomavirus (HPV) detected by DNA testing.
The diagnostic region of interest (ROI) from immediately adjacent sections were imaged, and the basal lamina and surface of the superficial layer were delimited. Nonoverlapping quantitatively stained nuclei were selected from 1,190 samples with histopathological characteristics of normal (929), koilocytosis (130), CIN 1 (40), CIN 2 (23), and CIN 3/carcinoma in situ (CIS) (68). A fully automatic procedure located and recorded the center of every nucleus in the region of interest (ROI). We used linear discriminant analysis to assess the changes between normal and CIN 3/CIS.
Scores computed from the cell-by cell features and the clinical grade of CIN/SIL were highly correlated, as were those of the architectural features and the clinical grade of CIN/SIL. We found even higher correlations between a combination of cell-by-cell and architectural scores, and clinical grade. Using these scores, we found MACs in the normal biopsy specimens from patients with high-grade CIN/SIL. Furthermore, the same scores correlated with the molecular detection of HPV.
Quantitative histopathology can be used in large clinical trials as an objective and reproducible measure of CIN/SIL. Detectable phenotypic changes correlate well with CIN/SIL neoplastic progression. It can also be used to infer the presence of CIN/SIL (MACs) and molecular changes associated with increased risk of cancer development (high-risk HPV).
作为评估用于宫颈肿瘤的新兴光学技术项目的一部分，我们团队正在对1190例患者的活检标本进行定量组织病理学分析。中期分析的目标是：（a）定量评估宫颈上皮内瘤变（CIN）/鳞状上皮内病变（SIL）的肿瘤进程；（b）检测恶性相关变化（MACs）；（c）对通过DNA检测发现的人乳头瘤病毒（HPV）进行表型测量。
对紧邻切片的诊断感兴趣区域（ROI）进行成像，并划定基底层和表层表面。从具有正常（929例）、空泡化（130例）、CIN 1（40例）、CIN 2（23例）和CIN 3/原位癌（CIS）（68例）组织病理学特征的1190个样本中选择不重叠的定量染色细胞核。一个全自动程序定位并记录感兴趣区域（ROI）内每个细胞核的中心。我们使用线性判别分析来评估正常与CIN Ⅲ/CIS之间的变化。
根据逐个细胞特征计算的分数与CIN/SIL的临床分级高度相关，根据结构特征计算的分数与CIN/SIL的临床分级也高度相关。我们发现逐个细胞分数与结构分数的组合与临床分级之间的相关性更高。使用这些分数，我们在高级别CIN/SIL患者的正常活检标本中发现了MACs。此外，相同的分数与HPV的分子检测相关。
定量组织病理学可用于大型临床试验，作为CIN/SIL的一种客观且可重复的测量方法。可检测到的表型变化与CIN/SIL肿瘤进展密切相关。它还可用于推断CIN/SIL（MACs）的存在以及与癌症发生风险增加相关的分子变化（高危HPV）。
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