Immunohistochemically demonstrated lymph node micrometastasis and prognosis in patients with otherwise node-negative hilar cholangiocarcinoma

OBJECTIVE: To investigate whether immunohistochemically demonstrated lymph node micrometastasis has prognostic significance in patients with histologically node-negative (pN0) hilar cholangiocarcinoma. SUMMARY BACKGROUND DATA: The clinical significance of immunohistochemically detected lymph node micrometastasis recently has been evaluated in various tumors. However, no reports have addressed this issue with regard to hilar cholangiocarcinoma. METHODS: A total of 954 lymph nodes from surgical specimens of 45 patients with histologically node-negative hilar cholangiocarcinoma who underwent macroscopically curative resection were immunostained with monoclonal antibody against cytokeratins 8 and 18. The results were examined for relationships with clinical and pathologic features and with patient survival. RESULTS: Lymph node micrometastases were detected immunohistochemically in 11 (24.4%) of the 45 patients, being found in 13 (1.4%) of 954 lymph nodes examined. Of the 13 nodal micrometastases, 11 (84.6%) were found in the N2 regional lymph node group rather than N1. Clinicopathologic features showed no associations with lymph node micrometastases. Survival curves were essentially similar between patients with and without micrometastasis. In addition, the grade of micrometastasis showed no effect on survival. The Cox proportional hazard model identified microscopic venous invasion, microscopic resection margin status, and histologic differentiation as significant prognostic factors in patients with pN0 disease. CONCLUSIONS: Lymph node micrometastasis has no survival impact in patients with otherwise node-negative hilar cholangiocarcinoma. The authors do not recommend extensive lymph node sectioning with keratin immunostaining for prognostic evaluation.     

Clinical significance of lymph node micrometastasis in gallbladder carcinoma

BACKGROUND: This retrospective study was intended to define the clinical significance of lymph node micrometastasis in gallbladder carcinoma. METHODS: A total of 1136 regional lymph nodes taken from 63 consecutive patients undergoing radical resection were examined histologically. Micrometastasis was defined as a metastasis missed on routine histologic examination with hematoxylin-and-eosin but detected by immunohistochemical examination with an antibody against cytokeratins 8 and 18. RESULTS: None of 9 patients (0%) with pT1 disease and 19 of 54 patients (35%) with pT2-4 disease had nodal micrometastases. Univariate analysis identified nodal micrometastasis, type of radical resection, M classification, pT classification, perineural invasion, pTNM stage, timing of radical resection, lymphatic vessel invasion, and pN classification as significant variables. Multivariate analysis revealed that nodal micrometastasis (P =.0003) and type of radical resection (P=.0044) were independent prognostic factors. Nodal micrometastasis affected survival adversely, despite the absence (P=.0002) or presence (P <.0001) of overt nodal metastasis. Nodal micrometastasis correlated significantly with invasive characteristics: lymphatic vessel invasion, perineural invasion, and distant metastasis. CONCLUSIONS: Lymph node micrometastasis is the strongest independent predictor of worse survival regardless of the overt nodal status and may indicate aggressive tumor biology among patients undergoing curative resection for gallbladder carcinoma.     

Significance of immunohistochemically demonstrated micrometastases to lymph nodes in esophageal cancer with histologically negative nodes

BACKGROUND: We examined the prevalence, patterns, and clinical significance of nodal micrometastases in patients with esophageal cancer. METHODS: Cervical, mediastinal, and abdominal lymph nodes systematically removed from 37 patients without conventional histologic evidence of lymph node metastasis from esophageal squamous cell carcinoma were immunohistochemically examined to detect cells that were stained for cytokeratins by the monoclonal antibody cocktail AE1/AE3. Postoperative care and survival were compared in cases with and without such micrometastases. RESULTS: Nodal micrometastases were found in 14 of 37 patients (38%). Among these patients, 9, 7, and 4 had micrometastases to abdominal, mediastinal, and cervical lymph nodes, respectively. Postoperative tumor recurrence was significantly more frequent in patients with micrometastases (50%) than in those without (9%, P = .008). Overall and relapse-free survival in the former group was significantly worse than in the latter group (P = .042 and P = .002, respectively). Nodal micrometastases had an independent prognostic importance for relapse-free survival as determined by multivariate analysis. CONCLUSIONS: Metastatic tumor cells are frequently present in lymph nodes, even in patients without histologic evidence of nodal metastasis from esophageal cancer. Nodal micrometastases indicates a poorer prognosis after a curative esophagectomy procedure in histologically node-negative cases.     

Prognostic effect of lymph node micrometastasis in patients with histologically node-negative gastric cancer

Background There is no consensus as to the impact of lymph node micrometastasis on survival of patients with gastric cancer. The aim of this study was to clarify the prognostic significance of lymph node micrometastasis in patients with histologically node-negative gastric cancer Methods Lymph nodes (n=2039) from 64 patients with histologically node-negative gastric cancer (T2, T3) were evaluated for micrometastasis. Three serial 5-μm sections of the resected lymph nodes were prepared for immunohistochemical staining with the anti-cytokeratin antibody CAM 5.2. Results Micrometastasis was found in 73 of 2039 nodes (4%) and 20 of 64 patients (32%). The 5-year survival rate was significantly lower for patients with lymph node micrometastasis than for those without lymph node micrometastasis (66% vs. 95%,P<.01). The 5-year survival rate was significantly lower when there were four or more positive micrometastatic nodes (94% vs. 29%,P <.01) and when there were extragastric micrometastatic nodes (89% vs. 53%,P<.01). Conclusions Lymph node micrometastasis was associated with poor outcome in patients with histologically node-negative gastric cancer. The number and the level of lymph node micrometastases are useful prognostic markers for deciding treatment strategies for additional therapy and follow-up.     

Significance of immunohistochemical nodal micrometastasis as a prognostic indicator in potentially curable oesophageal carcinoma

BACKGROUND: The number of positive lymph nodes is an important prognostic predictor in patients with oesophageal cancer. However, the significance of nodal micrometastasis in patients with overt nodal metastasis is unknown. The aim of this study was to clarify the clinical implications of nodal micrometastasis in patients undergoing curative oesophagectomy for oesophageal cancer. METHODS: Cervical, mediastinal and abdominal lymph nodes systematically removed from 104 patients with oesophageal cancer were examined immunohistochemically to detect cells that stained positively for cytokeratins with the monoclonal antibody cocktail AE1/AE3. The postoperative course and survival rates were compared among patients with and without micrometastases, after numerical classification of overt metastatic nodes (none, between one and four, five or more). RESULTS: Univariate analysis showed T stage, nodal micrometastasis and number of overt nodal metastases to be significant prognostic factors after oesophagectomy. Multivariate analysis revealed nodal micrometastasis and number of overt nodal metastases to be independent prognostic factors. The presence of micrometastases had a significant adverse effect on postoperative survival in patients with no overt metastasis and in patients with one to four overt metastatic nodes, but no such impact in patients with five or more overt metastatic nodes. CONCLUSION: Assessment of nodal status by both histological examination for overt metastases and immunohistochemical examination for micrometastases is useful in stratifying patients undergoing curative oesophagectomy.     

Immunohistochemically demonstrated lymph node micrometastasis and prognosis in patients with gallbladder carcinoma

OBJECTIVE: To investigate whether immunohistochemically demonstrated lymph node micrometastasis has a survival impact in patients with advanced gallbladder carcinoma (pT2-4 tumors). SUMMARY BACKGROUND DATA: The clinical significance of immunohistochemically detected lymph node micrometastasis recently has been evaluated in various tumors. However, few reports have addressed this issue with regard to gallbladder carcinoma. METHODS: A total of 1476 lymph nodes from 67 patients with gallbladder carcinoma (pN0, n = 40; pN1, n = 27) who underwent curative resection were immunostained with monoclonal antibody against cytokeratins 8 and 18. The results were correlated with clinical and pathologic features and with patient survival. RESULTS: Lymph node micrometastases were detected immunohistochemically in 23 (34.3%) of the 67 patients and in 37 (2.5%) of the 1476 nodes examined. Of the 37 nodal micrometastases, 21 (56.8%) were single-cell events, and the remaining 16 were clusters. Five micrometastases were detected in the paraaortic nodes. Clinicopathologic features showed no significant associations with the presence of lymph node micrometastases. Survival was worse in the 27 patients with pN1 disease than in the 40 with pN0 disease (5-year survival; 22.2% vs. 52.6%, P = 0.0038). Similarly, survival was worse in the 23 patients with micrometastasis than in the 44 without micrometastasis (5-year survival; 17.4% vs. 52.7%, P = 0.0027). Twenty-eight patients without any lymph node involvement had the best prognosis, whereas survival for the 11 patients with both types of metastasis was dismal. The grade of micrometastasis (single-cell or cluster) had no effect on survival. The Cox proportional hazard model identified perineural invasion, lymph node micrometastasis, and microscopic venous invasion as significant independent prognostic factors. CONCLUSIONS: Lymph node micrometastasis has a significant survival impact in patients with pN0 or pN1 gallbladder carcinoma who underwent macroscopically curative resection. Extensive lymph node sectioning with keratin immunostaining is recommended for accurate prognostic evaluation for patients with gallbladder carcinoma.     

Distribution of Lymph Node Metastasis Including Micrometastasis in Gastric Cancer with Submucosal Invasion

Abstract The purpose of this retrospective study was to analyze the distribution of lymph node metastases, including micrometastases, according to the location of the gastric cancer with submucosal invasion. A total of 118 patients with submucosal gastric cancer were enrolled in this study. The distribution of lymph node metastases was examined according to tumor location. Immunohistochemical examination using anti-cytokeratin antibody was performed to examine nodal micrometastases in 118 patients. Lymph node metastasis was found in 19.5% (23/118) of the patients. Significant differences were found for tumor size and depth, lymphatic invasion, and venous invasion for patients with and without nodal metastasis. The distribution of lymph node metastasis for tumors at upper or middle portions of the stomach was mainly found along the left gastric artery. The distribution of lymph node metastasis for tumors in the lower and lesser curvature varied. Immunohistochemical analysis found that 15 of 23 patients with lymph node metastasis found by histologic examination had micrometastases. The presence of two or more lymph node micrometastases was found in these 15 patients, and they were distributed in another stations, including distant nodes. The incidence of micrometastasis was 24.2% (23/95) in pN0 patients. Lymph node micrometastases were confined to regional nodes near the primary tumor. When planning minimally invasive treatment for submucosal gastric cancer, it is important to understand the distribution of lymph node metastasis, including micrometastasis, according to tumor location.     

Pattern of Lymph Node Micrometastasis and Prognosis of Patients with Colorectal Cancer

Background: Studies of lymph node micrometastases in patients with colorectal cancer have ignored the prognostic significance of the number and level of lymph node micrometastases. The aim of this study was to clarify the prognostic significance of the status of lymph node micrometastases in histologically node-negative colorectal cancer.Methods: We used immunohistochemistry with anti-cytokeratin antibody CAM5.2 to examine 1013 lymph nodes in 42 patients (12 recurrent and 30 nonrecurrent) with histologically determined Dukes B colorectal cancer. Five serial 6-m sections were used for immunohistochemical staining. The frequency, tumor cell pattern, and number and level of lymph node micrometastases were compared between the recurrent and nonrecurrent groups.Results: Micrometastasis was confirmed in 16% (59/373) of lymph nodes in the recurrent group and 12% (77/640) of lymph nodes in the nonrecurrent group, and the frequency of lymph node micrometastases was 92% (11/12) in the recurrent group and 70% (21/30) in the nonrecurrent group. The tumor cell pattern in the metastatic lymph nodes was similar in the recurrent and nonrecurrent groups. Micrometastasis in four or more lymph nodes occurred more frequently in the recurrent group than in the nonrecurrent group (58% vs. 20%, P < .05), and micrometastasis to N2 or higher nodes occurred more frequently in the recurrent group than in the nonrecurrent group (92% vs. 47%, P < .01).Conclusions: The number and level of positive micrometastatic lymph nodes was significantly correlated with postoperative recurrence of histologically determined Dukes B colorectal cancer. This parameter is a useful prognostic indicator in histologically node-negative colorectal cancer and is helpful in planning adjuvant chemotherapy.     

Immunohistochemistry analysis of micrometastasis in pretreatment lymph nodes from patients with esophageal cancer

BACKGROUND: With recent advances in neoadjuvant therapy in esophageal cancer, pretreatment lymph node staging has become increasingly important in stratifying patients to appropriate treatment regimens and for prognostication. Immunohistochemical analysis (IHC) using epithelial markers has been shown to identify micrometastases in histologically negative lymph nodes. We performed this study to evaluate if IHC analysis in thoracoscopic/laparoscopic (Ts/Ls) pretreatment staging lymph nodes can reveal additional diagnostic information to routine histopathology. METHODS: Specimens of 106 patients with esophageal cancer who had pretreatment Ts/Ls staging were retrospectively studied. Lymph node biopsies were obtained for IHC staining using cytokeratin (CK) of AE1/AE3. IHC staining for p53, an apoptosis protein associated with poor prognosis in esophageal cancer, was also performed. RESULTS: 331 Ts/Ls staging lymph node biopsies were collected from 106 patients. A total of 15.4% (51/331) of the lymph nodes or 34.9% (37/106) of patients were found to have metastatic deposits by routine histology. All the histologically positive lymph nodes were CK positive. Among the remaining 280 histologically negative lymph nodes, 11(3.9%) were found to have micrometastasis by CK staining. Three patients (4.3%, 3/69) were upstaged from N0 to N1. They died of early recurrences after treatment. A total of 67.6% (25/37) of the patients with histologically positive lymph node were p53 positive. No histologically negative lymph node was found to be p53 positive in this series. CONCLUSIONS: Immunohistochemical analysis for CK can detect micrometastatic involvement of lymph nodes that are missed on routine pathologic examination, and, therefore, can improve lymph node staging. Its clinical significance in esophageal cancer warrants further study.     

The Prognostic Significance of Micrometastases in Breast Cancer: A SEER Population-Based Analysis

Introduction The prognostic significance of lymph node micrometastases in breast cancer is controversial. We hypothesized that the survival of patients with solely micrometastatic disease (N1mi) would be intermediate to patients with 1–3 tumor-positive lymph nodes (N1) and those with no positive lymph nodes (N0). Methods We queried the surveillance, epidemiology and end results (SEER) database for all patients between 1992 and 2003 with invasive ductal or lobular breast cancer without distant metastases and ≤3 axillary nodes with macroscopic disease. Patients were stratified by nodal involvement and compared using the Kaplan–Meier method. Cox proportional hazards regression was utilized to compare survival after adjusting for patient and tumor characteristics. Results Between 1992 and 2003, N1mi diagnoses increased from 2.3% to 7% among the 209,720 study patients (p < 0.001). In a T-stage stratified univariate analysis, N1mi patients had a worse prognosis in T2 lesions. On multivariate analysis, N1mi remained a significant prognostic indicator across all patients (p < 0.0001) with a hazard ratio of 1.35 compared to N0 disease and 0.82 compared to N1 disease. Other negative prognostic factors included male gender, estrogen-receptor negativity, progesterone-receptor negativity, lobular histology, higher grade, older age, higher T-stage, and diagnosis in an earlier time period. Conclusion Nodal micrometastasis of breast cancer carries a prognosis intermediate to N0 and N1 disease, even after adjusting for tumor- and patient-related factors. Prospective study is warranted and the results of pending trials are highly anticipated. Until then adjuvant therapy trials should consider using N1mi as a stratification factor when determining nodal status.     

Lymph node micrometastases in early gastric cancer and their impact on prognosis

Abstract While the presence of lymph node metastases in early gastric cancer (EGC) is the most significant prognostic factor, the relevance of lymph node micrometastases remains uncertain. The authors studied 5400 lymph nodes dissected from 300 patients treated surgically for EGC between 1976 and 1999, all of whom were histologically pN0. Micrometastases were defined as single or small clusters of neoplastic cells identifiable only by immunohistochemical methods. Lymph node micrometastases were observed in 30 of the 300 patients (10%). No significant correlation was observed between micrometastases and other clinicopathological characteristics. Analysis of overall survival showed no significant difference between positive or negative micrometastasis groups. The results of our study show that the presence of lymph node micrometastases in EGC does not influence patient prognosis. Electronic Publication     

胃下部癌常规病理阴性第11P组淋巴结微转移的研究

目的 检测胃下部癌患者常规病理阴性第11P组淋巴结微转移的情况,分析淋巴结微转移与临床病理因素的关系.方法 应用连续切片法和端粒酶重复扩增-ELISA方法 检测43例胃下部癌常规病理阴性的43枚第11P组淋巴结,结合临床病理资料进行统计学分析. 结果 本组43例胃下部癌患者常规病理阴性第11P组淋巴结经连续切片法检出有4例4枚淋巴结发生微转移,微转移发生率为9%;应用端粒酶重复扩增-ELISA法检测微转移发生率为44%,其中包括应用连续切片法检测出有微转移的4枚淋巴结.端粒酶重复扩增-ELISA法微转移检出率明显高于连续切片法(x 2 =13.07,P<0.05).胃下部癌第11P组淋巴结微转移与原发肿瘤大小(x 2 =8.488,P<0.05)、浸润深度(x 2 =6.473,P<0.05)及临床分期(x 2 =12.022,P<0.05)有关,与患者年龄、性别、大体分型、组织分化程度尤关.结论 胃下部癌常规病理阴性第11P组淋巴结中存在较高的微转移发生率,其微转移发生率与原发肿瘤大小、浸润深度及临床分期有关.     

前列腺癌根治术前盆腔淋巴结微转移检测的研究

目的 明确新辅助治疗后前列腺癌根治术前,real-time PCR检测盆腔淋巴结微转移的意义.方法 2007年8月至2010年3月对21例临床局限性前列腺癌病例,根据病理检查阳性(A组)、real-time PCR检查前列腺特异性抗原(PSA)mRNA和前列腺特异性膜抗原(PSMA)mRNA阳性(B组)、病理检查及real-time PCR检查PSA mRNA及PSMA mRNA均阴性(C组)进行分组,D组为对照组.术前行淋巴管造影显示盆腔淋巴结,对可疑淋巴结在X线定位下穿刺抽吸淋巴液,用real-time PCR方法检测淋巴液中PSA mRNA和PSMA mRNA的表达,阳性表达提示淋巴结转移的存在,术后对淋巴结组织切片进行免疫组化检查.结果 对术前盆腔淋巴结穿刺抽吸淋巴液用real-time PCR方法检测PSA mRNA和PSMA mRNA的表达,证实有14例淋巴结存在微转移,术后对清扫淋巴结进行免疫组化检查有3例存在淋巴结转移,A组与B组PSA mRNA和PSMA mRNA的表达存在明显的差异;A、B组淋巴液中PSA mRNA及PSMA mRNA的表达明显高于淋巴结(P＜0.01).结论 采用real-time PCR方法检测淋巴液中PSA和PSMA mRNA的表达有利于探测到淋巴结微转移的存在,术前穿刺淋巴结抽吸淋巴液提高了术前前列腺癌分期的准确性.     

Clinical significance of molecular biological detection of micrometastases in gastric carcinoma]

Micrometastases are considered to be a cause of recurrence after curative surgery for gastric cancer. It is important to clarify the clinicopathologic characteristics of micrometastases in the lymph nodes and peritoneal cavity to determine the treatment options in gastric cancer. Two consecutive sections of lymph nodes from patients with various cancers were examined by simultaneous staining with ordinary hematoxylin and eosin (H & E) and immunostaining with anti-cytokeratin antibody, respectively. Micrometastases in the lymph nodes were found in 18% of mucosal cancer, 25% of submucosal cancer, and 65% of T3 (serosal) cancers pecimens, with cancer-free nodes examined by H & E staining. A reduced 5-year survival rate was demonstrated in patients with nodal micrometastases among those with submucosal cancer and those with T3 cancer and cancer-free nodes examined by H & E staining. Molecular biological detection (MBD) of micrometastasis in lavage cytology specimens was performed by RT-PCR of carcinoembryonic antigen mRNA or telomerase activity assay. MBD protocols revealed micrometastases in cases with negative cytology results. Survival analysis demonstrated peritoneal recurrences in MBD-positive cases, whereas there was no recurrence in MBD-negative cases. Peritoneal micrometastases detected by MBD protocols appear to be a significant risk factor for recurrence. Therefore indications for lymph node dissection and postoperative chemotherapy should be determined based on the findings of micrometastases in gastric cancer.     

早期黏膜下胃癌微转移和微浸润的临床意义

目的 探讨临床早期黏膜下胃癌的淋巴结微转移和原发灶微浸润的临床意义。方法 对79例早期黏膜下胃癌患者手术切除的1945个淋巴结及68例肿瘤原发灶分别进行连续超薄切片,并应用抗细胞角蛋白(CK)单克隆抗体(CAM5．2)进行免疫组化检测并结合临床病理学指标及患者预后进行综合分析研究。结果 常规HE染色时,淋巴结转移率为13％(10／79),而CK染色为34％(27／79)。早期黏膜下胃癌的微转移发生率为25％(17／69)。68例早期黏膜下胃癌患者中,微浸润的发生率为16％(11,／68)。淋巴结微转移分别多发于肿瘤直径大于2cm(43％),凹陷型(48％),淋巴管侵犯(73％)和深度黏膜下侵犯(53％)的肿瘤。微浸润多发于低分化癌(33％)和深度黏膜下侵犯(31％)的肿瘤。5年生存率在没有微转移的患者为100％,有微转移的患者为82％,有微浸润的患者为73％。结论 CK免疫组化检查在诊断微转移和微浸润上明显优于常规HE检查。淋巴结的微转移和原发灶的微浸润明显影响黏膜下胃癌患者预后。     

Clinical Significance of Lymph Node Micrometastasis in Ampullary Carcinoma

Background This study aimed to clarify the clinical significance of lymph node micrometastasis in ampullary carcinoma. Materials and Methods Pancreaticoduodenectomy with regional lymphadenectomy was performed for 50 consecutive patients with ampullary carcinoma. A total of 1,283 regional lymph nodes (median, 25 per patient) were examined histologically for metastases. Overt metastasis was defined as metastasis detected during routine histologic examination with hematoxylin and eosin. Micrometastasis was defined as metastasis first detected by immunohistochemistry with an antibody against cytokeratins 7 and 8. The median follow-up period was 119 months after resection. Results Overt metastasis was positive in 90 lymph nodes from 27 patients. Micrometastasis was positive in 33 lymph nodes from 12 patients, all of whom also had overt nodal metastases. Patients with nodal micrometastasis had a larger number of lymph nodes with overt metastasis (median, 3.5) than those without (median, 0; P < 0.001). Overt metastasis to distant nodes (superior mesenteric nodes, para-aortic nodes) was more frequent (P = 0.001 and P = 0.038, respectively) in patients with nodal micrometastasis. Nodal micrometastasis was found to be a strong independent prognostic factor on univariate (P < 0.0001) and multivariate (relative risk, 5.085; P = 0.007) analyses. From among the 27 patients with overt nodal metastasis, the outcome after resection was significantly worse in the patients with nodal micrometastasis (median survival time of 11 months) than in those without (median survival time of 63 months; P = 0.0009). Conclusions Immunohistochemically detected lymph node micrometastasis indicates intensive lymphatic spread, and thus adversely affects the survival of patients with ampullary carcinoma.     

Micrometastasis in lymph nodes and microinvasion of the muscularis propria in primary lesions of submucosal gastric cancer

BACKGROUND: It is important to clarify the clinicopathologic characteristics of micrometastasis in lymph nodes and microinvasion in primary lesions for the treatment options with regard to submucosal gastric cancer. METHODS: We examined 1945 lymph nodes and 68 primary tumors resected from 79 patients with submucosal gastric cancer. Two consecutive sections were prepared for simultaneous staining with ordinary hematoxylin and eosin and immunostaining with anticytokeratin antibody (CAM 5.2), respectively. RESULTS: The incidence of nodal involvement in 79 patients with submucosal gastric cancer increased from 13% (10/79 patients) by hematoxylin and eosin staining to 34% (27/79 patients) by cytokeratin immunostaining. Micrometastases in the lymph nodes were found in 17 of 69 patients (25%), with cancer-free nodes examined by hematoxylin and eosin. Microinvasion to the muscularis propria was found in 11 of 68 patients (16%) who were histologically diagnosed with submucosal gastric cancer. Survival analysis demonstrated a lesser 5-year survival in the patients with micrometastasis in lymph nodes (82%) and with microinvasion to muscularis propria (73%). A high incidence of nodal involvement was found in submucosal cancers of large size (> 2 cm; 43%), a depressed type (48%), lymphatic invasion (73%), and deeper submucosal invasion (submucosal 3, 53%). A higher incidence of microinvasion was found with the diffuse-type carcinoma (33%). CONCLUSIONS: Cytokeratin immunostaining is useful for detecting micrometastasis and microinvasion in submucosal gastric cancer. Tumor size, macroscopic type, lymphatic invasion, and the depth of submucosal invasion are strongly associated with lymph node involvement.     

Clinical value of genetically diagnosed lymph node micrometastasis for patients with oral squamous cell carcinoma

BACKGROUND: The purpose of this study was to investigate the incidence and clinical significance of genetically diagnosed lymph node micrometastasis for patients with oral squamous cell carcinoma (SCC). METHODS: A total of 495 lymph nodes obtained from 21 patients with primary oral SCCs that had p53 mutations were examined for corresponding p53 mutations in lymph nodes using mutant allele-specific amplification (MASA). RESULTS: Among 476 histologically negative nodes, 44 were scored as positive for metastasis by MASA. All 19 histologically positive lymph nodes were genetically positive. Four of the 10 pN0 cases and nine of the 11 pN-positive cases had genetically positive micrometastases. Four patients who had five or more genetically positive lymph nodes located in three or more levels, three with disease staged as pN0 or pN1, died of cancer. CONCLUSIONS: These results indicate that a high rate of micrometastasis in cervical lymph nodes of oral SCCs and patients with multiple or lower neck spread of micrometastases have a poor prognosis; they should be treated with postoperative adjuvant therapy.     

Intraoperative radioisotope sentinel lymph node mapping in non-small cell lung cancer

BACKGROUND: Lymph node metastases are the most significant prognostic factor in localized non-small cell lung cancer (NSCLC). Nodal micrometastases may not be detected. Identification of the first nodal drainage site (sentinel node) may improve detection of metastatic nodes. We performed intraoperative Technetium 99m sentinel lymph node (SN) mapping in patients with resectable NSCLC. METHODS: Fifty-two patients (31 men, 21 women) with resectable suspected NSCLC were enrolled. At thoracotomy, the primary tumor was injected with 2 mCi Tc-99. After dissection, scintographic readings of both the primary tumor and lymph nodes were obtained with a handheld gamma counter. Resection with mediastinal node dissection was performed and findings were correlated with histologic examination. RESULTS: Seven of the 52 patients did not have NSCLC (5 benign lesions, and 2 metastatic tumors) and were excluded. Forty-five patients had NSCLC completely resected. Mean time from injection of the radionucleide to identification of sentinel nodes was 63 minutes (range 23 to 170). Thirty-seven patients (82%) had a SN identified; 12 (32%) had metastatic disease. 35 of the 37 SNs (94%) were classified as true positive with no metastases found in other intrathoracic lymph nodes without concurrent SN involvement. Two inaccurately identified SNs were encountered (5%). SNs were mediastinal (N2) in 8 patients (22%). CONCLUSIONS: Intraoperative SN mapping with Tc-99 is an accurate way to identify the first site of potential nodal metastases of NSCLC. This method may improve the precision of pathologic staging and limit the need for mediastinal node dissection in selected patients.