Prognostic significance of immunohistochemically detected lymph node micrometastases in pT0N0 esophageal squamous cell carcinoma

Chao, Yin‐Kai; Yeh, Chi-Ju; Chuang, Wen-Yu; Fan, Kang‐Hsing; Hsieh, Ming‐Ju; Chu, Yen-Chang; Cheng, Ann‐Joy; Hui-ping, Liu

doi:10.1002/jso.21362

Cited by 10 publications

(18 citation statements)

References 15 publications

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“…There is a strong body of evidence suggesting that immunohistochemically detected micrometastatic deposits in oesophageal cancer are associated with reduced survival and increased risk of disease recurrence [55][56][57][58][59][60][61][62][63][64][65]. Several studies have identified micrometastatic spread to be an independent prognostic indicator in oesophageal adenocarcinoma [35,39,41,43,66] and it has been postulated that these micrometastatic deposits may help to explain why up to 50% of histologically nodenegative oesophageal cancer patients develop recurrence, despite a curative resection of the primary tumour [67,68].…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Lymph node metastases and prognosis in oesophageal carcinoma – A systematic review

Kayani

Zacharakis

Ahmed

et al. 2011

European Journal of Surgical Oncology (EJSO)

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Oesophageal cancer is the seventh most common cause of cancer-related death in the developed world and the incidence of oesophageal adenocarcinoma is now the fastest growing of any gastrointestinal cancer. Lymph node involvement is the single most important prognostic factor in oesophageal cancer. Imaging to determine the extent of lymph node involvement and plan treatment often requires a combination of modalities to avoid under-staging. The seventh edition of the staging system released by the International Union Against Cancer (IUCC) has stratified lymph node involvement according to the number of lymph nodes involved and redefined its groupings for location of metastatic lymph node involvement. This review discusses the prognostic and treatment implications of these modifications and explores micrometastatic lymph node involvement, capsular infiltration and lymph node ratio as possible additions to the staging system.

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Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Lymph node metastases and prognosis in oesophageal carcinoma – A systematic review

Kayani

Zacharakis

Ahmed

et al. 2011

European Journal of Surgical Oncology (EJSO)

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“…On the other hand, it has been reported that micrometastases, including an individual cancer cell and clustered tumor cells, could be a prognostic factor in EC . Cytokeratin (CK) immunohistochemistry (IHC) using antibody AE1/AE3 is a common method to detect micrometastases in lymph nodes . However, the clinical significance of the number of occult MLNs remains unclear because of the complexity of the procedure to detect occult MLNs.…”

Section: Introductionmentioning

confidence: 99%

“…3,4 Cytokeratin (CK) immunohistochemistry (IHC) using antibody AE1/AE3 is a common method to detect micrometastases in lymph nodes. [5][6][7] However, the clinical significance of the number of occult MLNs remains unclear because of the complexity of the procedure to detect occult MLNs. There is also a report that single cells cannot proliferate in lymph nodes because they have already been killed by local and general immunocytes.…”

Section: Introductionmentioning

confidence: 99%

The impact of the number of occult metastatic lymph nodes on postoperative relapse of resectable esophageal cancer

et al. 2013

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Clinical stage II/III esophageal cancer (EC), as defined by the Japanese Classification, relapses at a moderately high rate even after curative resection. The number of lymph node metastases is known to be associated with tumor relapse. Recently, the prognostic significance of occult metastatic lymph nodes (MLNs), as well as that of overt MLNs, has been reported. The aim of this study was to investigate the impact of the total number of MLNs including occult MLNs on postoperative relapse in clinical stage II/III EC. One hundred and five patients with clinical stage II/III EC who underwent esophagectomy accompanied by radical lymphadenectomy at the Department of Surgical Oncology in Osaka City University Hospital between January 2000 and October 2008 were included in this study. Occult MLNs, metastases not detected by hematoxylin-eosin staining, were identified by immunohistochemistry (IHC) using antipancytokeratin antibody AE1/AE3. The clinicopathological features of occult MLNs were compared between the relapse and no relapse groups. A total of 6558 lymph nodes (1357 from two-field dissection and 5201 from three-field dissection) were examined by IHC staining; 362 overt MLNs and 143 occult MLNs were detected. The number of occult MLNs increased in proportion to the International Union Against Cancer pathological (p)N-status and pStage. When the number of occult MLNs was added to the number of pNs, the number of total MLNs was associated with postoperative relapse. With respect to tumor, node, metastasis stage, 6 of 22 patients (27%) who were pathological node-negative converted to node-positive by considering total MLNs. The number of N3 patients with relapse increased markedly with restaging by total MLNs. The number of total MLNs, but not overt MLNs, was an independent prognostic factor on multivariate analysis. These results suggest that occult MLNs were often found, and they were associated with postoperative relapse of resectable esophageal cancer. The total number of MLNs including occult MLNs could contribute to evaluating the precise stage of patients with esophageal cancer.

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“…Nonetheless, the inability to identify residual tumor cells in surgical specimens should by no means be considered as a synonymous of cure because up to one third of such patients will ultimately develop disease recurrences . To date, there have been only a few studies that have attempted to identify the main risk factors for disease recurrence …”

Section: Introductionmentioning

confidence: 99%

“…[4][5][6][7][8] To date, there have been only a few studies that have attempted to identify the main risk factors for disease recurrence. 9,10 The diagnosis of pCR is established by pathological examination of the resected specimens using routine hematoxylin and eosin (H&E) staining. However, consensus criteria for guiding the pathological examination in patients with esophageal cancer who receive nCRT have not yet been established.…”

Section: Introductionmentioning

confidence: 99%

Association between the thoroughness of the histopathological examination and survival in patients with esophageal squamous cell carcinoma who achieve pathological complete response after chemoradiotherapy

Chen

Wen

et al. 2015

Dis Esophagus

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The College of American Pathologists guidelines recommend examining at least four representative tumor blocks for determining pathological T stage in patients with primarily resected esophageal cancer. Whether the same pathological requirements are adequate in patients undergoing esophagectomy following neoadjuvant chemoradiotherapy (nCRT) remains unclear. We hypothesized that current examination protocols may underestimate the presence of microscopical residual disease after nCRT, potentially leading to under-staging. We retrospectively reviewed the records of patients with esophageal squamous cancer (ESCC) who were diagnosed as having pathological complete response (pCR) following nCRT. The thoroughness of the pathological examination in pCR patients was examined using (i) the number of blocks examined in suspicious tumor area (≤4 vs. >4), and (ii) the block quotient (calculated as the pretreatment tumor length divided by the number of blocks examined in suspicious tumor area). A total of 91 patients were enrolled. The mean number of blocks used to confirm pCR was 4.8 (range: 2-14). The 5-year overall survival (OS) and disease-free survival (DFS) in the entire cohort were 55% and 65%, respectively. Multivariate analyses identified the block quotient as the only independent predictor of OS and DFS. Receiver operating characteristic curve analysis indicated an optimal cutoff value of 1.4 for the block quotient. Among the patients who achieved pCR, the 5-year DFS differed significantly between subjects with a low (≤1.4) or high (>1.4) block quotient (76% vs. 47%, respectively, P = 0.03). The block quotient (calculated by the pretreatment tumor length divided by the number of blocks) - which reflects the meticulousness of the histopathological examination for confirming pCR - is associated with survival in ESCC patients.

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Prognostic significance of immunohistochemically detected lymph node micrometastases in pT0N0 esophageal squamous cell carcinoma

Abstract: LNMs are uncommon in pathological complete responders but hold prognostic significance.

Cited by 10 publications

References 15 publications

Lymph node metastases and prognosis in oesophageal carcinoma – A systematic review

Lymph node metastases and prognosis in oesophageal carcinoma – A systematic review

The impact of the number of occult metastatic lymph nodes on postoperative relapse of resectable esophageal cancer

Association between the thoroughness of the histopathological examination and survival in patients with esophageal squamous cell carcinoma who achieve pathological complete response after chemoradiotherapy

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