Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
Mod Pathol. 2012 Aug;25(8):1128-39. doi: 10.1038/modpathol.2012.61. Epub 2012 Apr 6.
Recent literature suggests an increasing incidence of colorectal carcinoma in young patients. We performed a histologic, molecular, and immunophenotypic analysis of patients with sporadic early-onset (≤40 years of age) colorectal carcinoma seen at our institution from the years 2000-2010 and compared these tumors to a cohort of consecutively resected colorectal carcinomas seen in patients >40 years of age. A total of 1160 primary colorectal adenocarcinomas were surgically resected for the years 2000 through 2010. Of these, 75 (6%) were diagnoses in patients ≤40 years of age of which 13 (17%) demonstrated abnormalities in DNA mismatch repair, 4 (5%) were in patients with known germline genetic disorders (two patients with familial adenomatous polyposis, one patient with juvenile polyposis, and one patient with Li-Fraumeni syndrome), and three patients (4%) had long-standing chronic inflammatory bowel disease. The sporadic early-onset colorectal carcinoma group comprised a total of 55 patients (55/1160, 5%) and were compared with a control group comprising 73 consecutively resected colorectal carcinomas with proficient DNA mismatch repair in patients >40 years of age. For the early-onset colorectal carcinoma group, most cases (33/55, 60%) were diagnosed between the age of 35 and 40 years of age. Compared with the control group, the early-onset colorectal carcinoma group was significantly different with respect to tumor location (P<0.007) with 80% (44/55 cases) identified in either the sigmoid colon (24/55, 44%) or rectum (20/55, 36%). Morphologically, early-onset colorectal carcinomas more frequently displayed adverse histologic features compared with the control colorectal carcinoma group such as signet ring cell differentiation (7/55, 13% vs 1/73, 1%, P=0.021), perineural invasion (16/55, 29% vs 8/73, 11%, P=0.009) and venous invasion (12/55, 22% vs 4/73, 6%, P=0.006). A precursor adenomatous lesion was less frequently identified in the early-onset colorectal carcinoma group compared with the control group (19/55, 35% vs 39/73, 53%, P=0.034). Of the early-onset colorectal carcinomas, only 2/45 cases (4%) demonstrated KRAS mutations compared with 11/73 (15%) of the control group colorectal adenocarcinomas harboring KRAS mutations, although this difference did not reach statistical significance (P=0.13). BRAF V600E mutations were not identified in the early-onset colorectal carcinoma group. No difference was identified between the two groups with regard to tumor stage, tumor size, number of lymph node metastases, lymphatic invasion, tumor budding, mucinous histology, or tumor-infiltrating lymphocytes. Both groups had similar recurrence-free (P=0.28) and overall survival (P=0.73). However, patients in the early-onset colorectal carcinoma group more frequently either presented with or developed metastatic disease during their disease course compared with the control colorectal carcinoma group (25/55, 45% vs 18/73, 25%, P=0.014). In addition, 8/55 patients (15%) in the early-onset colorectal carcinoma group developed local recurrence of their tumor while no patients in the control colorectal carcinoma group developed local recurrence (P<0.001), likely due to the increased incidence of rectal carcinoma in the patients with early-onset colorectal carcinoma. Our study demonstrates that colorectal carcinoma is not infrequently diagnosed in patients ≤40 years of age and is not frequently the result of underlying Lynch syndrome or associated with other cancer-predisposing genetic conditions or chronic inflammatory conditions. These tumors have a striking predilection for the distal colon, particularly the sigmoid colon and rectum and are much more likely to demonstrate adverse histologic factors, including signet ring cell differentiation, venous invasion, and perineural invasion.
最近的文献表明，年轻患者的结直肠癌发病率不断增加。我们对 2000 年至 2010 年在我院就诊的散发型早发（≤40 岁）结直肠癌患者进行了组织学、分子和免疫表型分析，并将这些肿瘤与>40 岁的连续切除的结直肠癌患者进行了比较。在 2000 年至 2010 年期间，共对 1160 例原发性结直肠腺癌进行了手术切除。其中，75 例（6%）诊断为≤40 岁的患者，其中 13 例（17%）显示 DNA 错配修复异常，4 例（5%）为已知种系遗传疾病患者（两例家族性结肠腺瘤性息肉病患者、一例青少年息肉病患者和一例 Li-Fraumeni 综合征患者），3 例（4%）为长期慢性炎症性肠病患者。散发型早发性结直肠癌组共 55 例（55/1160，5%），与>40 岁且 DNA 错配修复功能良好的 73 例连续切除的结直肠癌患者的对照组进行比较。早发性结直肠癌组中，大多数病例（33/55，60%）的诊断年龄在 35-40 岁之间。与对照组相比，早发性结直肠癌组在肿瘤部位方面有显著差异（P<0.007），80%（44/55 例）位于乙状结肠（24/55，44%）或直肠（20/55，36%）。形态学上，早发性结直肠癌与对照组相比，具有更多不良的组织学特征，如印戒细胞分化（7/55，13%比 1/73，1%，P=0.021）、神经周围侵犯（16/55，29%比 8/73，11%，P=0.009）和静脉侵犯（12/55，22%比 4/73，6%，P=0.006）。早发性结直肠癌组中腺瘤性前驱病变的检出率明显低于对照组（19/55，35%比 39/73，53%，P=0.034）。早发性结直肠癌组中，只有 2/45 例（4%）显示 KRAS 突变，而对照组中 73 例结直肠腺癌中有 11 例（15%）携带 KRAS 突变，尽管这种差异没有达到统计学意义（P=0.13）。BRAF V600E 突变在早发性结直肠癌组中未被发现。两组在肿瘤分期、肿瘤大小、淋巴结转移数、淋巴管浸润、肿瘤芽生、黏液组织学或肿瘤浸润淋巴细胞方面无差异。两组患者的无复发生存率（P=0.28）和总生存率（P=0.73）相似。然而，与对照组相比，早发性结直肠癌组患者在疾病过程中更常出现或发展为转移性疾病（25/55，45%比 18/73，25%，P=0.014）。此外，早发性结直肠癌组中有 8/55 例（15%）患者发生肿瘤局部复发，而对照组中无患者发生局部复发（P<0.001），这可能是由于早发性结直肠癌患者中直肠癌的发病率较高。本研究表明，结直肠癌在≤40 岁的患者中并不少见，且不是 Lynch 综合征的常见结果，也与其他癌症易感性遗传疾病或慢性炎症性疾病无关。这些肿瘤对远端结肠有明显的偏好，特别是乙状结肠和直肠，并且更有可能表现出不良的组织学特征，包括印戒细胞分化、静脉侵犯和神经周围侵犯。
