Immunohistochemical detection of lymph node‐DTCs in patients with node‐negative HNSCC

Abstract

This study was performed to systematically assess the prevalence, topography and prognostic impact of disseminated tumor cells (DTCs) in lymph nodes (LN) of patients with primary, regional and distant metastasis-free head and neck squamous cell carcinoma (HNSCC) who underwent resection with elective neck dissection. From the routinely processed resection specimen, we could prospectively analyze a total of 1.137 exactly mapped LNs of 50 pN0-HNSCC patients, classified as tumor free by routine histopathology. Three immunohistochemistry (IHC) assays using antibodies directed against CK5/14, a broad spectrum of CKs (1-8, 10, 14-16 and 19), and CD44v6, respectively, were applied on 4.190 LN sections to detect DTCs. The IHC results were correlated with clinicopathologic parameters and clinical follow-up data. We detected seven micrometastases (MM) in five patients and 31 DTCs in 12 patients. Overall, 15 (30%) patients were positive for DTCs or MMs. Strikingly, the anatomical distribution of LN affected with DTCs was not random, but was dependent on the lateralization of the primary tumor and clustered significantly most proximal to the primary tumor. None of the investigated patients developed loco-regional lymphatic or distant metastasis during the mean follow-up period of 71 months. Our results reveal clinically occult tumor cell dissemination as an early and frequent event in HNSCC. Considering that higher rates of recurrences in therapeutic LN dissection concepts have been reported than in elective neck dissection strategies, our DTC-data support to perform elective neck dissections, since they appear to be effective in preventing loco-regional lymphatic recurrence from LN DTCs or MMs.

A specific agonist of the orphan nuclear receptor NR2F1 suppresses metastasis through the induction of cancer cell dormancy

“…To address this, we stained patient samples for NR2F1 in normal adjacent epithelium, primary tumors, and lymph nodes that were confirmed to have solitary HNSCC DTCs but not over metastasis [21]. Pancytokeratin was used as a marker to identify cells of epithelial origin in all tissues [22]. Cells were scored as NR2F1 hi , NR2F1 med , or NR2F1 −/low .…”

“…The copyright holder for this preprint this version posted February 2, 2021. ; https://doi.org/10.1101/2021.01.30.428967 doi: bioRxiv preprint nodes that were confirmed to have solitary HNSCC DTCs but not over metastasis [21]. Pancytokeratin was used as a marker to identify cells of epithelial origin in all tissues [22]. Cells were scored as NR2F1 hi , NR2F1 med , or NR2F1 -/low .…”

Clinical Significance of Metastasis or Micrometastasis to the Lymph Node Along the Superior Mesenteric Vein in Gastric Carcinoma: A Retrospective Analysis

“…According to the 6 th edition of International Union Against Cancer (UICC), lymph node metastasis (LNM) is classified into isolated tumor cells (ITC), micrometastasis (MI), and macrometastasis (MA), depending on the size of the metastatic deposit (5). Methods to investigate the presence of MI vary, from serial slices with hematoxylin and eosin (H&E) staining, immunohistochemical (IHC) staining, to real-time reverse transcription-polymerase chain reaction (RT-PCR) (6)(7)(8)(9). Cytokeratin is one component of the cytoskeleton of epithelial cells that is not present in normal lymph nodes, and its corresponding antibody is widely used to detect minute deposits of tumor cells in lymph nodes by IHC staining.…”

The necessity of IIb dissection in T1–T2N0M0 oral squamous cell carcinoma: protocol for a randomized controlled trial

“…However, if we only pursue a higher survival rate, most patients will be regarded as 'overtreated'. At present, the technique for detecting occult metastatic lymph nodes in the neck is still imprecise; we can detect susceptible nodes only by physical examination, B-scan ultrasonography, and enhanced computed tomography (CT)/magnetic resonance imaging (MRI), but diagnoses obtained by these methods are far from precise [2,3]. Studies have shown that the rate of occult metastasis in the early stages of oral cancer is about 30% [1,4,5], meaning that nearly 70% of patients with negative nodes underwent neck dissection during routine treatment.…”