Các yếu tố tiên đoán trong ung thư đại trực tràng
Tóm tắt
Bối cảnh.— Dưới sự chỉ dẫn của College of American Pathologists, trạng thái hiện tại của hiểu biết về các yếu tố tiên đoán bệnh lý (các yếu tố liên quan đến kết quả) và các yếu tố dự đoán (các yếu tố dự đoán phản ứng với điều trị) trong ung thư đại trực tràng đã được đánh giá. Một nhóm đa ngành gồm các chuyên gia lâm sàng (bao gồm các chuyên ngành ung thư y học, ung thư phẫu thuật và ung thư xạ trị), bệnh lý và thống kê về ung thư đại trực tràng đã xem xét tất cả tài liệu y khoa liên quan và phân loại các yếu tố tiên đoán được báo cáo thành các danh mục phản ánh sức mạnh của bằng chứng đã công bố chứng minh giá trị tiên đoán của chúng. Theo đó, các danh mục các yếu tố tiên đoán sau đã được xác định. Danh mục I bao gồm các yếu tố được chứng minh rõ ràng là có tầm quan trọng tiên đoán dựa trên bằng chứng từ nhiều thử nghiệm đã công bố có tính thống kê mạnh mẽ và thường được sử dụng trong quản lý bệnh nhân. Danh mục IIA bao gồm các yếu tố đã được nghiên cứu rộng rãi về mặt sinh học và/hoặc lâm sàng và nhiều lần được chứng minh có giá trị tiên đoán cho kết quả và/hoặc giá trị dự đoán cho liệu pháp có tầm quan trọng đủ để được đưa vào báo cáo bệnh lý nhưng vẫn cần được xác thực trong các nghiên cứu thống kê mạnh mẽ. Danh mục IIB bao gồm các yếu tố đã được chứng minh là hứa hẹn trong nhiều nghiên cứu nhưng thiếu đủ dữ liệu để đưa vào danh mục I hoặc IIA. Danh mục III bao gồm các yếu tố chưa được nghiên cứu đủ để xác định giá trị tiên đoán của chúng. Danh mục IV bao gồm các yếu tố được nghiên cứu kỹ càng và được chứng minh là không có ý nghĩa tiên đoán.
Nguyên liệu và Phương pháp.— Tài liệu y khoa đã được xem xét một cách chặt chẽ, và phân tích đã chỉ ra các điểm cụ thể về sự biến đổi trong cách tiếp cận đã ngăn cản việc so sánh trực tiếp giữa các nghiên cứu đã công bố và ảnh hưởng đến chất lượng dữ liệu tổng hợp. Các danh mục về sự biến đổi được công nhận bao gồm các điểm sau: (1) phương pháp phân tích, (2) diễn giải phát hiện, (3) báo cáo dữ liệu và (4) đánh giá thống kê. Các điểm biến đổi bổ sung trong các danh mục này đã được xác định từ kinh nghiệm tổng hợp của nhóm. Các lý do để phân loại từng yếu tố tiên đoán vào danh mục I, II, III hoặc IV (các danh mục được xác định theo mức độ xác thực khoa học) đã được chỉ ra với tham chiếu đến các loại sự biến đổi cụ thể liên quan đến dữ liệu hỗ trợ. Đối với mỗi yếu tố và danh mục sự biến đổi liên quan đến yếu tố đó, các khuyến nghị chi tiết cho cải tiến đã được đưa ra. Các khuyến nghị được dựa trên các mục tiêu sau: (1) tăng cường sự đồng nhất và đầy đủ của đánh giá bệnh lý đối với mẫu khối u, (2) nâng cao chất lượng dữ liệu cần thiết để đánh giá xác định giá trị tiên đoán của từng yếu tố tiên đoán và (3) cuối cùng, cải thiện chăm sóc bệnh nhân.
Kết quả và Kết luận.— Các yếu tố được xác định có giá trị đưa vào danh mục I bao gồm: mức độ khu vực khối u được đánh giá qua bệnh lý (danh mục pT của hệ thống phân loại TNM của American Joint Committee on Cancer và Union Internationale Contre le Cancer [AJCC/UICC]); di căn hạch bạch huyết khu vực (danh mục pN của hệ thống phân loại TNM); xâm lấn mạch máu hoặc mạch bạch huyết; khối u còn lại sau phẫu thuật với mục đích chữa trị (phân loại R của hệ thống phân loại AJCC/UICC), đặc biệt liên quan đến các bờ phẫu thuật dương tính; và mức tăng kháng nguyên carcinoembryonic trước phẫu thuật (một yếu tố được xác lập bởi các phương pháp y học phòng thí nghiệm thay vì bệnh lý giải phẫu). Các yếu tố trong danh mục IIA bao gồm: mức độ khối u, trạng thái bờ radian (đối với các mẫu cắt bỏ với bề mặt không được phúc mạc hóa), và khối u còn lại trong mẫu cắt bỏ sau điều trị neoadjuvant (danh mục ypTNM của hệ thống phân loại TNM của AJCC/UICC). Các yếu tố trong danh mục IIB bao gồm: kiểu mô học, các đặc điểm mô học liên quan đến sự không ổn định microsatellite (MSI) (tức là phản ứng lympho của chủ thể đối với khối u và kiểu mô học tủy hay nhầy), mức độ MSI cao (MSI-H), mất đồng hợp tử tại 18q (mất allele gen DCC), và cấu trúc bờ khối u (biên xâm lấn so với biên đẩy). Các yếu tố được nhóm vào danh mục III bao gồm: hàm lượng DNA, tất cả các dấu hiệu phân tử khác ngoại trừ mất đồng hợp tử 18q/DCC và MSI-H, xâm lấn quanh thần kinh, mật độ mạch máu nhỏ, protein hoặc carbohydrate liên kết với tế bào khối u, xơ hóa quanh khối u, phản ứng viêm quanh khối u, phân biệt nội tiết thần kinh cục bộ, các vùng tổ chức hạt nhân và chỉ số tăng sinh. Các yếu tố thuộc danh mục IV bao gồm kích thước khối u và cấu hình khối u đại thể. Báo cáo này ghi lại những phát hiện và khuyến nghị của nhóm hội nghị đồng thuận, được tổ chức theo các hướng dẫn cấu trúc được xác định ở đây.
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Tannapfel, 1995, Expression of nm23-H1 predicts lymph node involvement in colorectal carcinoma., Dis Colon Rectum, 38, 651, 10.1007/BF02054128
Wang, 1993, Mutation in the nm23 gene is associated with metastasis in colorectal cancer., Cancer Res, 53, 717
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Takebayashi, 1996, Angiogenesis as an unfavorable prognostic factor in human colorectal carcinoma., Cancer, 78, 226, 10.1002/(SICI)1097-0142(19960715)78:2<226::AID-CNCR6>3.0.CO;2-J
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Saclarides, 1994, Tumor angiogenesis and rectal cancer., Dis Colon Rectum, 37, 921, 10.1007/BF02052599
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Bromley, 1996, A comparison of proliferation markers (BrdUrd, KI-67, PCNA) determined at each cell position in the crypts of normal human colonic mucosa., Eur J Histochem, 40, 89
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Mayer, 1993, The prognostic significance of proliferating cell nuclear antigen, epidermal growth factor receptor, and mdr gene expression in colorectal cancer., Cancer, 71, 2454, 10.1002/1097-0142(19930415)71:8<2454::AID-CNCR2820710805>3.0.CO;2-2
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Sahin, 1994, Assessment of Ki-67-derived tumor proliferation activity in colorectal adenocarcinomas., Mod Pathol, 7, 17
Neoptolemos, 1995, Cyclin/proliferation cell nuclear antigen immunohistochemistry does not improve the power of Dukes' or Jass' classifications for colorectal cancer., Br J Surg, 82, 184, 10.1002/bjs.1800820214
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Frank, 1995, Tumor angiogenesis as a predictor of recurrence and survival in patients with node-negative colon cancer., Ann Surg, 222, 695, 10.1097/00000658-199512000-00002