Lymph node staging in colorectal cancer:Old controversies and recent advances

Outcome prediction based on tumor stage reflected by the American Joint Committee on Cancer(AJCC)/Union for International Cancer Control(UICC)tumor node metastasis(TNM)system is currently regarded as the strongest prognostic parameter for patients with colorectal cancer.For affected patients,the indication for adjuvant therapy is mainly guided by the presence of regional lymph node metastasis.In addition to the extent of surgical lymph node removal and the thoroughness of the pathologist in dissecting the resection specimen,several parameters that are related to the pathological work-up of the dissected nodes may affect the clinical significance of lymph node staging.These include changing definitions of lymph nodes,involved lymph nodes,and tumor deposits in different editions of the AJCC/UICC TNM system as well as the minimum number of nodes to be dissected.Methods to increase the lymph node yield in the fatty tissue include methylene blue injection and acetone compression.Outcome prediction based on the lymph node ratio,defined as the number of positive lymph nodes divided by the total number of retrieved nodes,may be superior to the absolute numbers of involved nodes.Extracapsular invasion has been identified as additional prognostic factor.Adding step sectioning and immunohistochemistry to the pathological work-up may result in higher accuracy of histological diagnosis.The clinical value of more recent technical advances,such as sentinel lymph node biopsy and molecular analysis of lymph nodes tissue still remains to be defined.     

TNM staging, molecular staging and prognostic factors of rectal cancer]

Pathologic evaluation of the resected specimen is a critical component when managing the patients with rectal cancer, from initial diagnosis through definitive treatment. The best estimation of prognosis in rectal cancer is related to the anatomic extent of disease determined by pathology. Although a large number of staging system has been developed for rectal cancer over the years, use of TNM staging system of the AJCC (American Joint Committee on Cancer) and the UICC (International Union Against Cancer) are gaining popularity among the colorectal surgeons. Multiple genetic alterations are the prerequisite for carcinogenesis including rectal cancer. Although numerous molecular markers are investigated in relation to prognosis or response to therapy of rectal cancer, those molecular markers could not provide sufficient evidence for the incorporation of available prognostic biomarkers into clinical practice. In this article, the evolution of staging system of rectal cancer and its prognostic relevance are reviewed comprehensively.     

Analysis of neuroendocrine differentiation and the p53/BAX pathway in UICC stage III colorectal carcinoma identifies patients with good prognosis

Background and aims Neuroendocrine differentiation is an independent prognostic factor in colorectal cancer. Moreover, an altered p53/BAX pathway is associated with a poor clinical outcome in Union Internationale Contre le Cancer (UICC) stage III disease. Because these markers are involved in different genetic events disrupted in colorectal cancer, we investigated the prognostic power of a multimarker analysis.Patients and methods Specimens were analyzed from 59 patients with UICC stage III disease who underwent surgery for colorectal adenocarcinoma at our institution and were followed up for 5 years or until death. Tumors were studied for both p53 mutation and BAX protein expression as well as for the expression of neuroendocrine markers. Statistical analysis of each marker alone or in combination was performed.Results p53 status/BAX expression and neuroendocrine differentiation are not correlated in stage III colorectal cancers. However, the combination of both independent events identified a subgroup of patients with an excellent prognosis: Patients whose tumors were neuroendocrine marker-negative and who exhibited an intact p53/BAX pathway lived longer (mean survival, 93 months; range, 82–104 months) than patients whose tumors were either neuroendocrine marker-positive or whose tumors had a completely disrupted apoptotic pathway (41 months; range, 26–57 months; p<0.00001). In multivariate regression analysis, neuroendocrine marker-positive, p53 mutated, low-BAX-expressing tumors revealed an almost fivefold higher risk for earlier death (p<0.0001).Conclusion Disruption of the p53/BAX pathway is not pathognomonic for colorectal cancers with neuroendocrine differentiation. Both represent independent prognostic markers in UICC stage III disease. Therefore, the combined analysis of p53 status, BAX expression and neuroendocrine differentiation allows one to identify subgroups of patients with either very good or very poor prognosis.P. Grabowski and I. Sturm contributed equally to this work     

Ⅰ/Ⅱ期食管癌术后局部复发的临床研究

目的在AJCC/UICC食管癌第八版TNM病理分期系统指导下,分析Ⅰ/Ⅱ期食管鳞癌根治术后局部复发情况,指导临床。方法回顾分析2012年1月至2017年8月我院胸外科收治的212例Ⅰ/Ⅱ期食管癌术后患者的临床资料,统计分析局部复发率及影响因素。结果本组患者ⅠA、ⅠB、ⅡA、ⅡB期局部复发率分别为0.00%、8.86%、18.57%、25.00%,腹部复发率2.44%。单因素分析肿瘤T分期(χ²=8.434,P=0.038)、病理分期(χ²=9.942,P=0.019)是影响Ⅰ/Ⅱ期食管癌术后患者局部复发的临床因素,差异有统计学意义,但是病理分期的无复发生存曲线较T分期分离更好。多因素分析提示术后病理分期是影响局部复发的独立预后影响因素,差异有统计学意义(P=0.004,HR=2.054,95%CI 1.258~3.352)。结论AJCC/UICC食管癌第八版TNM分期是局部复发的独立预后因素,Ⅱ期患者局部复发率较高,应该给予术后干预。     

Neuroendocrine differentiation is a relevant prognostic factor in stage III-IV colorectal cancer

OBJECTIVE: To determine the prognostic relevance of neuroendocrine differentiation in colorectal cancer. METHODS: The survival of 116 patients with colorectal cancer of stages III (n = 59) and IV (n = 57) was correlated with the extent of neuroendocrine differentiation. Chromogranin A and synaptophysin were used as neuroendocrine markers. Based on the degree of immunoreactivity for these markers, tumours were classified as 0 (no expression of neuroendocrine markers), 1 (< 2% cells staining positive for neuroendocrine markers) and 2 (> 2% cells staining positive for neuroendocrine markers). Patients were followed up for more than 5 years or until death. RESULTS: Seven of 59 (11.8%) stage III cancers and 13/57 (22.8%) stage IV cancers belonged to group 2. The 96 patients of groups 0 and 1 lived for 48.9 months, whereas the 20 patients of group 2 survived for only 18.6 months (Kaplan-Meier survival curves, P < 0.001). The difference was most striking in stage III disease with 79.4 months' survival for combined groups 0 and 1, and 38.9 months' survival for group 2 (P < 0.01). Using the multivariate Cox regression model, the presence of more than 2% of cells with neuroendocrine differentiation was found to be an independent prognostic parameter for stage III and IV disease. No correlation was observed between neuroendocrine differentiation and tumour location, grade, depth of invasion or stage. CONCLUSION: Neuroendocrine differentiation is often seen in colorectal cancer. It is an independent prognostic factor in stage III-IV colorectal cancer.     

Prognostic significance of calcium-binding protein S100A4 in colorectal cancer

BACKGROUND & AIMS: Prognostication in colon cancer almost exclusively still rests on the tumor stage. Furthermore, tumor-derived markers to improve discrimination of low- and high-risk subtypes generally are not in use. S100A4 has been reported to be associated with invasion and metastasis; however, no data are available on its prognostic value in colorectal carcinoma. Therefore, we investigated the prognostic significance of immunohistochemical S100A4 expression in colorectal carcinoma compared with clinicopathologic parameters and expression of cell-cycle markers p16, p21, p27, p53, Ki-67, and RB. METHODS: Archival tissue from 709 patients with colorectal cancer were retrieved, applied in tissue array technology, and investigated immunohistochemically. Univariate and multivariate survival analyses were carried out on all investigated parameters. RESULTS: Sixteen percent of cases showed high; 31%, low; and 53%, no S100A4 expression. In Kaplan-Meier analysis, S100A4 positively stained cases showed a significantly decreased survival time compared with negatively stained cases (P < 0.0001). In multivariate regression analysis, S100A4 expression emerged as a highly significant independent parameter (P < 0.001) with the highest relative-risk factor among other covariates. Nodal status (pN) lost its prognostic value if S100A4 was added to the model. High S100A4 expression was associated with tumor stage pT3/4, secondary metastasis, women, p16, and RB expression. CONCLUSIONS: S100A4 expression represents a highly significant prognostic marker in colorectal carcinoma, which is able to identify a subset of patients at high risk. In this respect, it is superior to established prognostic markers such as nodal status, pT stage, and p53 expression.     

Transforming growth factor—β1in invasion and metastasis in colorectal cancer

AIM：To investigate the role of TGFβ1 in invasion and metastasis in colorectal cancer by analysing TGFβ1 correlated wity depth of tumor invasion,stage and metastasis.METHODS:Serum TGFβ1levels were determined in50patients with colorectal cancer and 30healthy volunteers using a TGFβ1 enzyme-linked immunosorbent assay.TGFβ1 expression in primary and lymph node metastatic lesions were detected in 98cases of colorectal cancer by immunohistochemical staining and in situ hybridization.RESULTS:Serum levels of TGFβ1 in patients with colorectal cancer(40&#177;18μg&#183;L^-1)were significantly higher than those in the healthy control group(19&#177;8μg&#183;L^-1),P&lt;0.05.Elevated levels of serum TGFβ1were found in 60%of patients with colorectal cancer when the mean+2s was used as the upper limit of the normal range(35.1μg&#183;L^-1).Increases in serum TGFβ1 levels were significantly asociated with Dukei‘s stage(P&lt;0.05),but there was no significant difference between,Duki‘s stage Bpatients and Dukei‘s stage Cpatients.In the cytoplasm of cancer cells,TGFβ1 was immunostained in37.8%(37/98)of colorectal cancer,and this expression was confirmed by in situ hybridization,Among35cases of colorectal cancer with lymph node metastatic lesions,TGFβ1 positive staining was found in18(51.4%)cases of primary tumor,and 25(71.4%)cases with lymph node metastatic lesions,respectively,Of17cases with no staining in the primary lesion.7(41.2%)casesshowed TGFβ1 staining in the metastatic lesion.Serum TGFβ1 levels and TGFβ1 expression in colorectal cancer tissues were correlated significantly with depth of tumor invasion,stage and metastasis,Patients in stage C-D,T3-T4and with metastasis had significantly higher TGFβ1 levels than patients in stage A-B,T1-T2and without metastasis(P&lt;0.05).CONCLUSION:These results suggest that transforming growth factor-β1 is closely related to the invasion and metastasis of colorectal cancer.It increased the invasive and metastatic potential of tumor by altering a tumor microenvironment.TGFβ1 may be used as a possible biomarke.     

Transforming growth factor-b1 in invasion and metastasis in colorectal cancer

AIM: To investigate the role of TGF β1 in invasion andmetastasis in colorectal cancer by analysing TGFβ1correlated with depth of tumor invasion, stage andmetastasis.METHODS: Serum TGFβ1 levels were determined in 50patients with colorectal cancer and 30 healthyvolunteers using a TGFβ1 enzyme-linkedimmunosorbent assay.TGFβ1 expression in primary andlymph node metastatic lesions were detected in 98cases of colorectal cancer by immunohistochemicalstaining and in situ hybridization.RESULTS: Serum levels of TGFβ1 in patients with colorectalcancer(40+ 18 μg @ L-1) were significantly higher thanthose in the healthy control group(19+8 μg @ L-1),P＜0.05. Elevated levels of serum TGFβ1 were found in60 % of patients with colorectal cancer when the mean+2 s was used as the upper limit of the normal range(35.1 μg @ L-1). Increases in serum TGFβ1 levels weresignificantly associated with Dukei's stage (P＜0.05),but there was no significant difference between Dukei'sstage B patients and Dukei's stage C patients. In thecytoplasm of cancer cells, TGFβ1 was immunostainedin 37.8 % (37/98) of colorectal cancer, and thisexpression was confirmed byin situ hybridization.Among 35 cases of colorectal cancer with lymph nodemetastatic lesions, TGFβ1 positive staining was foundin 18 (51.4 %) cases of primary tumor, and 25 (71.4%) cases with lymph node metastatic lesions,respectively. Of 17 cases with no staining in theprimary lesion, 7 (41.2%) casesshowed TGFβ1staining in the metastatic lesion. Serum TGFβ1 levelsand TGFβ1 expression in colorectal cancer tissues werecorrelated significantly with depth of tumor invasion,stage and metastasis. Patients in stage C-D,T3-T4 andwith metastasis had significantly higher TGFβ1 levelsthan patients in stage A-B,T1-T2 and withoutmetastasis (P＜0.05).CONCLUSION: These results suggest that transforminggrowth factor-β1 is closely related to the invasion andmetastasis of colorectal cancer. It increased theinvasive and metastatic potential of tumor by alteringa tumor microenvironment. TGFβ1 may be used as apossible biomarker.     

Thymidylate synthase and cyclin d1 protein expression in lymph node negative colorectal cancer: role as prognostic factors?

Background/Aims: Thymidylate synthase (TS) is an enzyme for DNA-synthesis and the target for 5-fluorouracil whereas cyclin-D1 plays a critical role in the progression of cells through the G1 phase of the cell-cycle. There is evidence that expression of these markers may predict the outcome of patients with colorectal cancers. The aim of this study was to examine the prognostic value of TS and cyclin D1 protein expression in patients with node negative colorectal cancers. Methodology: TS and cyclin D1 protein expression from 140 patients with UICC stage I and II colorectal cancer was analyzed by immunhistochemistry in paraffin-embedded primary tumour specimens. Results: The 1-, 5- and 10-year overall-survival rates were 96%, 86% and 71%, respectively. Tumour stage and recurrence were associated with overall-survival. Low- and high TS immunoreactivity was present in 68 (48%) and 72 (52%) of cancers, respectively. Low- and high cyclin D1 immunoreactivity was present in 98 (70%) and 42 (30%) of the cancers, respectively. Patients (n=72) with high TS expressing tumours had a worse overall-survival than patients (n=68) with low TS expressing colorectal cancers (p=0.011). No difference in overall-survival was seen between patients with high and low cyclin D1 expressing cancers. Conclusions: TS may be helpful as a prognostic marker in lymph node negative colorectal cancer.     

Multivariate analysis of clinical,operative and pathologic features of esophageal cancer: who needs adjuvant therapy?

The failure of adjuvant therapy to significantly improve the prognosis of patients undergoing esophago-gastrectomy for cancer may be because of poor patient selection. We sought prognostic factors that would identify those patients who could benefit from adjuvant therapy. Data on 15 possible prognostic factors were prospectively collected on 225 patients undergoing esophago-gastrectomy at a single institution, and univariate and multivariate analyzes performed. T, N, M and overall UICC stage, differentiation, involvement of the circumferential resection margin and number of metastatic of lymph nodes were identified as significant prognostic factors by univariate analysis. Multivariate analysis revealed that the completeness of resection (R-category), ratio of metastatic to total nodes resected and the presence of vascular invasion were independently significant prognostic factors. Following R0 or R1 resection, patients with a metastatic to total lymph node ratio > 0.2 and /or the presence of vascular invasion have a poor prognosis, and the effects of adjuvant therapy in these patients should be studied.     

Thymidine phosphorylase, dihydropyrimidine dehydrogenase and thymidylate synthase mRNA expression in primary colorectal tumors—correlation to tumor histopathology and clinical follow-up

Aim Evaluation of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), and thymidylate synthase (TS) mRNA levels in formalin-fixed, and paraffin-embedded tissues of patients with colorectal cancer and their prognostic and/or predictive value.Materials and methods Total RNA was isolated from microdissected, formalin-fixed, and paraffin-embedded tissues (controls and tumor) and subjected to quantitative RT-PCR (QRT-PCR) in the LightCycler system. Resulting mRNA levels correlated to tumor histology (n=102) and the clinical follow-up in patients treated by resection alone (n=40) and by resection plus adjuvant 5-FU-based chemotherapy (n=52).Results Correlation to histopathological parameters revealed a significant association between tumor stage and the TP mRNA level (T and N category and UICC) as well as the TP:DPD (T and N category and UICC) and TS:DPD (T category) ratio. In addition, tumor differentiation was correlated to the TS mRNA level and the TS:DPD ratio. Finally, the TS:DPD ratio was a prognostic marker for overall survival in patients receiving resection alone (p=0.032). Moreover, a high TP:DPD ratio (>8.1; p=0.002) and, marginally, low DPD (<8.2; p=0.05) mRNA levels significantly correlated to disease-free survival.Conclusion We present a novel, standardized approach for TP, DPD, and TS mRNA quantification in archival tissue specimens and applied this to a large series of primary colorectal tumors. Correlations to histopathological parameters and clinical follow-up revealed an association of TP, DPD and TS mRNA expression patterns with tumor stage and suggested new prognostic and predictive markers for patients with colorectal cancer.     

Histogenesis and prognostic value of myenteric spread in colorectal cancer: a Japanese multi-institutional study

Background

The histogenesis of the pattern of cancer spread along Auerbach’s plexus (myenteric spread: MS) remains unclear and its prognostic value in colorectal cancer (CRC) has not been thoroughly investigated.

Methods

Pathology slides of 2845 pT2/pT3/pT4 CRCs stained with hematoxylin–eosin (H&E) were reviewed at 10 institutions. MS was classified into 2 groups depending on whether it was accompanied by the finding of perineural invasion (PN) within the lesion. In addition, immunohistochemical staining (D2-40, S100, CD56, synaptophysin) was performed for serially sectioned specimens from 50 CRCs diagnosed as having PN-negative MS.

Results

MS was observed in 504 patients (17.7 %); 360 patients were classified as having PN-positive MS and 144 as having PN-negative MS. The 5-year disease-free survival rate of patients with MS was lower than that of patients without MS (63.3 vs 82.7 %, P < 0.0001); however, there was no significant difference in survival outcome according to the presence or absence of intralesion PN in MS. Multivariate analysis showed that the prognostic impact of MS was independent of conventional prognosticators including T and N stages, vascular invasion and extramural PN. In all the tumors having PN-negative MS, remnants of neural tissue were identified within or around cancer nests located at the leading edge of MS.

Conclusions

MS is an important prognostic factor for CRC. This feature is the result of cancer development with replacement of Auerbach’s plexus and can be classified as intramural PN. The clinical significance of “Pn1” in the UICC/AJCC TNM classification could be enhanced by individual assessment both intramurally and extramurally.     

Calcium-sensing receptor A986S polymorphism in human rectal cancer

BACKGROUND AND AIMS: In vivo and in vitro experiments show the protective role of calcium ions (Ca2+) against colorectal cancer. The calcium-sensing receptor (CaSR) detects extracellular Ca2+ concentration. An association between the CaSR A986S polymorphism and serum calcium in healthy adults has been reported. Subjects with AA genotype had lower serum concentrations of Ca2+ than other genotypes. The expression of erbB-2, epidermal growth factor receptor (EGFR), p53, and ras in colorectal cancer has been suggested to have diagnostic and prognostic significance. PATIENTS AND METHODS: We investigated the relationship between the CaSR A986S polymorphism and the expression of erbB-2, EGFR, p53, and ras as well as the UICC stage in 56 patients with rectal cancer. RESULTS: The occurrence of the genotype AA was not different in cancer patients and in 112 controls. In the presence of the coexpression of major oncogenes, patients with genotype AA were in significantly higher UICC stages than in the case of AS genotype. During the follow-up period AA genotype showed a tendency for poor prognosis. CONCLUSIONS: Our observation raises the possibility that genetic alterations of CaSR influence the pathogenesis of rectal cancer.     

Outcome of urinary bladder recurrence after partial cystectomy for en bloc urinary bladder adherent colorectal cancer resection

Purpose

Around 10 % of colorectal cancers are locally advanced at diagnosis. There are higher incidences for sigmoid and rectal cancer adhered to urinary bladder (UB) rather than other segments of colon cancer. Surgeons often performed partial cystectomy as possible for preservation of patient’s life quality. This study investigates prognostic factors in patients who underwent bladder preservation en bloc resection for UB adherent colorectal cancer.

Methods

From 2000 to 2011, 123 patients with clinically UB involvement colorectal cancer underwent primary colorectal cancer with urinary bladder resection. Seventeen patients were excluded because of the concurrent distant metastasis at diagnosis and another 22 patients were excluded because of total cystectomy with uretero-ileal urinary diversion. Finally, 84 patients with clinical stage IIIC (T4bN0M0, according to AJCC 7th edition) that underwent en bloc colorectal cancer resection with partial cystectomy were enrolled into this study for further analysis.

Results

Preoperative colovesical fistula and positive CT result were significantly more in the urinary bladder invasion group (p?=?0.043 and 0.010, respectively). Pathological UB invasion is an independent predictor of intravesical recurrence (p?=?0.04; HR, 10.71; 95 % CI?=?1.12～102.94) and distant metastasis (p?=?0.016; HR, 4.85; 95 % CI?=?1.34?～?17.53) in multivariate analysis.

Conclusions

For bladder preservation en bloc resection of urinary bladder adherent colorectal cancer, the pathological urinary bladder invasion is significantly associated with more urinary bladder recurrence and distant metastasis. This result helps surgeons make decisions at surgical planning and establish follow-up protocol.     

Evaluation of UICC TNM classification for pancreatic cancer

Summary Conclusion A different stage grouping of TNM factors can improve the predictivity of the UICC TNM classification for pancreatic cancer. Nevertheless, the Japanese Pancreas Society (JPS) classification maintains a higher prognostic value. Background The use of a reliable staging classification facilitates the evaluation of anticancer treatments and the correct management of patients. The aim of the present study was to evaluate the prognostic value of three modified UICC TNM classifications, obtained by different stage grouping of the UICC TNM factors, comparing their predictivity to the standard UICC and the JPS classifications. Methods Clinical material consisted of 228 patients who underwent resection for pancreatic cancer. The reliability of the classifications was analyzed by the following methods: univariate analysis of stage survival curves; multivariate analysis of each classification after adjusting for grading and radicality; and correlation between the patients' distribution in the stages of each classification and in survival classes. Results The following modfiied UICC classification allowed a better differentiation of stage II and III survival (P=0.08) than standard UICC (p=0.74): stage I: T1N0M0; stage II: T1N1M0/T2N0M0: stage III: T2N1M0/T3 any NM0; stage IV: M1. The JPS classification better discriminated between the different stages (P<0.001). All classifications had an independent prognostic value by multivariate analysis. The correlation between stages and survival classes was higher for the JPS classification than either UICC TNM classification or the modified UICC classifications.     

The clinical significance of vascular invasion in colorectal cancer

A number of investigators have examined the influence of vascular invasion by tumor in colon, rectal, and colorectal cancer. Some consider the presence of vascular invasion an unfavorable prognostic feature and propose treatment recommendations based on its presence. Vascular invasion has two distinct components: blood vessel invasion and lymphatic vessel invasion. The use of elastic tissue stains enhance both the detection of blood vessel invasion and its differentiation from lymphatic vessel invasion. Almost all series report an increased incidence of blood vessel invasion with increasing stage and grade. Although the influence of blood vessel invasion and lymphatic vessel invasion on patterns of failure is variable, both are associated with a decrease in survival; however, treatment recommendations based solely on the presence of blood vessel invasion or lymphatic vessel invasion should be made with caution.     

结直肠癌组织HHLA2、 TMIGD2表达及其临床病理意义

目的 探讨结直肠癌组织中人内源性逆转录病毒-H长末端重复关联蛋白2(HHLA2)、跨膜和免疫球蛋白结构域2(TMIGD2)表达及其与患者临床病理特征及预后的关系.方法 选取2016年10月至2017年10月于北京老年医院住院治疗的168例结直肠癌患者(结直肠癌组);选取结直肠癌患者相应癌旁正常组织作为对照组.采用免疫组...     

Serological response to human endogenous retrovirus K in melanoma patients correlates with survival probability

A few years ago, reactivation of human endogenous retrovirus K (HERV-K) proviruses in melanoma was described. The expression of HERV-K proteins induces humoral immune responses. The aim of the present study was to elucidate the prognostic relevance of serological anti-HERV-K reactivity in melanoma patients. In a retrospective study, anti-HERV-K Gag and Env antibodies were detected in 51 of the 312 randomly selected and blinded sera from melanoma patients, but not in any of the 70 sera from healthy controls. Comparing serological HERV-K reactivity with established melanoma markers revealed a significant correlation (p = 0.018, Chi-square test) with the stage of disease classified according to the American Joint Committee on Cancer (AJCC). Anti-HERV-K reactivity was elevated in patients with acrolentiginous/mucosal/uveal melanoma (tumor subtypes developing at sun-protected sites) compared to patients with lentigo/nodular/superficial spreading melanoma (p = 0.011, Chi-square test). Patients with anti-HERV-K antibodies had a significantly decreased disease-specific overall survival (stage I-IV, p < 0.001; stage I-III, p = 0.005, log-rank test). Significantly, multivariate Cox regression analysis including prognostic markers in clinical use (e.g., AJCC stage, T-class, serum level of S100-beta) revealed serological HERV-K reactivity as an independent marker of reduced survival probability (p = 0.027) in melanoma patients with the early stages of the disease (AJCC I-III). This is the first report that the humoral anti-HERV-K immune response may provide additional prognostic information to that of established melanoma markers.     

癌组织及外周血中CD44、PLCEl、甲基化Sept9基因及DNA错配修复蛋白表达水平与结直肠癌病理分期及预后的相关性分析

目的探讨癌组织及外周血中白细胞分化抗原分化簇第44号(CD44)、磷酯酶Cεl(PLCEl)、甲基化Sept9基因及DNA错配修复蛋白表达水平与结直肠癌病理分期及预后的相关性。方法将2013年3月至2015年5月在西宁市第二人民医院确诊为结直肠癌的56例患者设为观察组,将同期于我院体检的55名健康成年人设为对照组。比较两组甲基化Sept9基因、CD44、PLCEl及DNA错配修复蛋白表达情况,分析以上指标在结直肠癌患者中的临床分布特点并进行相关性检验,比较不同甲基化Sept9基因、CD44、PLCEl及DNA错配修复蛋白表达情况并分析其与结直肠癌患者的预后相关性。结果观察组甲基化Sept9基因及CD44表达阳性率、PLCEl表达阴性率、DNA错配修复蛋白表达缺失率高于对照组(P<0.05)。甲基化Sept9基因、PLCEl及DNA错配修复蛋白在不同肿瘤浸润深度、肿瘤大小、病理分期及有无淋巴结转移结直肠癌患者中的表达差异有统计学意义(P<0.05)。CD44在不同肿瘤浸润深度、病理分期及有无淋巴结转移结直肠癌患者中的表达差异有统计学意义(P<0.05)。PLCEl与结直肠癌的浸润深度、病理分期呈负相关(r=-0.367,P=0.045;r=-0.522,P=0.008);甲基化Sept9基因与浸润深度、病理分期、淋巴结转移呈正相关(r=0.715,P=0.026;r=0.471,P=0.032;r=0.453,P=0.010),CD44与浸润深度、病理分期、淋巴结转移呈正相关(r=0.349,P=0.007;r=0.591,P=0.022;r=0.452,P=0.027),DNA错配修复蛋白与病理分期﹑淋巴结转移呈负相关(r=-0.487,P=0.041;r=-0.551,P=0.030)。不同CD44、甲基化Sept9基因、PLCEl及DNA错配修复蛋白表达情况的结直肠癌患者3年生存率差异有统计学意义(P<0.05)。PLCEl、DNA错配修复蛋白与结直肠癌患者3年生存率呈正相关(r=0.574,P=0.041;r=0.478,P=0.037),甲基化Sept9基因与结直肠癌患者3年生存率呈负相关(r=-0.515,P=0.034)。结论CD44、PLCEl、甲基化Sept9基因及DNA错配修复蛋白均与结直肠癌的病理分期相关,其检测有助于了解疾病的恶性程度,评估患者预后。     

Comparison of the sixth,seventh, and eighth editions of the American Joint Committee on Cancer Tumor-Node-Metastasis staging system for gastric cancer: A single institution experience

In 2018, the eighth edition of the American Joint Committee on Cancer Tumor-Node-Metastasis classification and staging system was implemented. Few reports were made comparing the performance of different editions of the American Joint Committee on Cancer (AJCC) system. Therefore, this study aimed to examine the prognostic predictability from the sixth to the eighth editions of the AJCC staging system for gastric cancer.A total of 414 patients with gastric cancer who underwent surgery at Changhua Christian Hospital from January 2007 to December 2017 were enrolled in the study. To identify the prognostic factors for gastric cancer death, univariate and multivariate analyses were performed. The homogeneity and discrimination abilities of the sixth to eighth editions of the staging system were compared using the likelihood ratio chi-square test, linear trend chi-square test, and Akaike information criterion.The sixth edition of the staging system had the lowest Akaike information criterion value, suggesting a better prognostic stratification than other editions. From the result of the likelihood ratio chi-square test, the T and N staging systems of the seventh and eighth editions had better homogeneity and discriminatory ability than the sixth edition. The eighth edition had better prognostic performance in patients at stage III compared with the seventh edition.The AJCC seventh and eighth editions had improved prognostic predictability of the T and N factors compared with the sixth edition. However, the overall staging performance of the eighth edition is not superior compared to the sixth edition. Further studies with larger sample size should be conducted to compare the performance of different editions of the AJCC staging system for different ethnic populations.