The clinical value of serum squamous cell carcinoma antigens 1 and 2 in head and neck squamous cell carcinoma

Objective

The usefulness of pretreatment measurement of SCC antigen in patients with head and neck SCC is still controversial. Our aim of this study was to evaluate the clinical usefulness of serum SCC antigen, SCCA1 and SCCA2 in the management of patients with head and neck SCC.

Proliferating cell nuclear antigen counts as markers of cell proliferation in head and neck cancer

Proliferating cell nuclear antigen (PCNA) expression was investigated immunhistochemically in 53 squamous cell carcinomas of the head and neck. PCNA is a 36-kDa nuclear protein associated with the cell cycle. Results were compared with Ki67 counts, with this latter marker used to demonstrate proliferative compartments. Overall, the PCNA and Ki67 labelling index showed a similar distribution pattern in normal and tumor tissue. A strong correlation was found to histological differentiation. There was no significant difference between PCNA and Ki67 counts (r = 0.8), and PCNA immunostaining allowed assessment of proliferative activity in the head and neck cancers studied. The application of formalin-fixed, paraffin-embedded tumor material demonstrated the advantage of this method and showed that it is an excellent alternative to Ki67 counts.     

头颈部鳞癌及癌旁组织端粒酶活性检测

目的：研究原发头颈部鳞癌及相关癌旁组织中端粒酶活性表达,探讨春作为头颈部鳞癌分子生物学标志物的可能性。方法：采用ＴＲＡＰ－ＰＣＲ－ＥＬＩＳＡ,对３２例原发头颈部鳞癌及１５例癌旁组织进行端粒酶活性检测。结果：３２例原发头颈部鳞癌中,２７例端粒酶活化,阳性率为８４．４％;１５例癌旁组织中５例端粒酶活化,阳性率为３３．３％。有淋巴结累及者端粒酶阳性率（８６．７％）高于无淋巴结累及者（８２．４％）,低分化     

Proteolytic patterns of head and neck squamous cell carcinoma

The significance of plasminogen activators and matrix metalloproteases for clinical outcome, growth and metastatic behavior of head and neck squamous cell carcinoma (SCC) is still controversial. The majority of studies has been based on either immunohistological stainings, which provide only limited quantitative information, or in vitro experiments. We analyzed 44 head and neck SCC and 11 mucosa tissue samples for the expression of gelatinolytic or fibrinolytic proteases by quantitative zymographic analysis and compared lytic activities to clinical and histopathological data. We calculated activation ratios for matrix metalloproteinases-2 and –9 (MMP-2 and MMP-9) by separate evaluations of inactive and activated MMP forms. Increased gelatinolytic and fibrinolytic activity was found in head and neck SCC when compared to mucosa. Increased values were caused by MMP-9 and urokinase type plasminogen activator, respectively. No statistically significant correlations of either protease lytic activity or activation ratio could be related to T-stage, metastasis, tissue necrosis or the differentiation stage of tumors. The data recorded are compared with previously published reports. Received: 27 August 1998 / Accepted: 6 January 1999     

头颈部鳞癌端粒酶活性的定量检测

目的：了解头颈部鳞癌及其颈淋巴结转移癌端粒酶的表达情况,探讨粒酶活性定量分析在头颈鳞癌诊断中的价值。方法：采用端粒重复序列液体闪烁计数法检测端粒酶活性。共检测取自２５例头颈部鳞癌患者的组织样本５５份,其中７例患者同时取有原发癌及其颈淋巴结转移癌两份样本,以２３份正常组织为对照。结果：①３２份原发鳞癌组织中端粒酶活性（ｃｐｍ值）在１０００以上的２８份,除２份外,均明显高于正常组织;２３份正常组织的端     

Second primary squamous cell carcinoma arising in cutaneous flap reconstructions of two head and neck cancer patients

Early complications of myocutaneous flap transfers following surgical eradication of head and neck tumors have been extensively described. However, knowledge concerning long-term complications of these techniques remains limited. We report the cases of two patients with a prior history of squamous cell carcinoma of the head and neck (HNSCC), who developed a second primary SCC on the cutaneous surface of their flaps, years after reconstruction. Interestingly, it seems that the well-known risk of a second primary SCC in patients with previous head and neck carcinoma also applies to foreign tissues implanted within the area at risk. Given the important expansion of these interventions, this type of complication may become more frequent in the future. Therefore, long-term follow-up of patients previously treated for HNSCC not only requires careful evaluation of the normal mucosa of the upper aero-digestive tract, but also of the cutaneous surface of the flap used for reconstruction.     

Synchronous squamous cell carcinoma and malignant lymphoma in the head and neck region

Synchronous malignancy of squamous cell carcinoma (SCC) and malignant lymphoma (ML) in the head and neck region is extremely rare. Here, we report the case of a 57-year-old man with a right-sided neck mass; he was referred to our hospital in September 2001. A series of staging work-ups revealed that he was simultaneously affected by oropharyngeal SCC and nasopharyngeal ML. He underwent conventional radiotherapy, and both the primary tumors showed complete remission. The metastatic lymph nodes showed poor response to the radiotherapy, and the patient was surgically salvaged by modified radical neck dissection. Although systemic chemotherapy against ML was scheduled, he refused the treatment and died of disseminated ML. It is essential to determine the lesion that should be given priority treatment in case of double primary malignancies; this can be facilitated by determining the prognosis of each malignancy.     

Proliferative activity following induction chemotherapy in squamous cell carcinoma of the head and neck

Summary Forty-six patients with advanced head and neck squamous cell carcinomas received two courses of chemotherapy with cisplatinum and bleomycin before undergoing cancer surgery. After surgery, histological serial sections of the resection specimens were examined. Biopsies from each resected specimen were shock-frozen for immunohistochemical examinations using the monoclonal antibodies Ki-67 and RPN-511, which are associated with cell proliferation. In no case did the morphologic analysis demonstrate complete tumor regression after chemotherapy. Thirty-seven patients showed partial tumor regressions histologically, as seen by tumor shrinkage of more than 50%. Nine of the specimens showed only minor regressions, with shrinkage less than 50%. The immunostaining of the frozen sections revealed in all cases the expressions of the Ki-67 nuclear antigen and the presence of specific transferrin (RPN-511) receptors in the proliferative compartments of the carcinomas.Presented at the annual meeting of the Austrian Society of Otorhinolaryngology-Head and Neck Surgery (Österreichische Gesellschaft für Hals-, Nasen-, Ohrenheilkunde, Kopf- und Halschirurgie), 14–18 September 1988, Feldkirch, Austria Offprint requests to: R. Bettinger     

Tumour-associated macrophages secrete IL-6 and MCP-1 in head and neck squamous cell carcinoma tissue

Conclusion. Tumour-associated macrophages (TAMs) in head and neck squamous cell carcinomas (HNSCCs) secrete interleukin 6 (IL-6) and monocyte chemotactic protein (MCP-1) that can be down-regulated by L-leucine-methylester (LLME); however, there is no qualitative difference between function of TAMs and tissue macrophages in mucosa as measured by IL-6 and MCP-1 secretion. Objectives. TAMs play an important role in the interaction with tumour cells in malignant tumours. The cells in the tumours that are the main sources of the various signal substances need to be further elucidated. The aim of this investigation was to reveal whether TAMs in HNSCCs secrete IL-6 and MCP-1. These cytokines influence tumour cell growth and macrophage influx in tumours, respectively. Materials and methods. In order to inhibit macrophage function in F-spheroids, in some experiments the tissue fragments were initially incubated with LLME, a substance that selectively inhibits function of phagocytes. IL-6 and MCP-1 secretion from untreated F-spheroids was compared to cytokine secretion from LLME-treated F-spheroids as measured by ELISA. Results. LLME did not affect the viability of F-spheroids and reduced IL-6 and MCP-1 secretion from monocyte-derived macrophages in vitro. F-spheroids from LLME-treated tissue fragments showed lower IL-6 and MCP-1 secretion compared with F-spheroids from tissue fragment untreated with LLME.     

Results of selective neck dissection in the primary management of head and neck squamous cell carcinoma

Selective neck dissection (SND) is known to be a valid procedure to stage the clinically N0 neck but its reliability to control metastatic neck disease remains controversial. This study analysed if selective neck dissection is a reliable procedure to prevent regional metastatic disease in head and neck squamous cell carcinoma (HNSCC). We retrospectively analysed the medical records of 163 previously untreated patients with squamous cell carcinoma of the oral cavity, oropharynx, larynx and hypopharynx treated initially in our departement from January 1990 to December 2002. All patients had unilateral or bilateral SND, in combination with surgical resection of the primary tumour. SND was performed in 281 necks. Finally, 146 patients who underwent 249 SND (39 I–III, I–IV, 210 II–IV, II–V) had adequate follow-up and were assessed for the regional control. The median follow-up was 37 months (1–180 months). The end points of the study were neck control following SND and overall survival. Twenty-five percent (30/119) of patients staged cN0 had lymph node (LN) metastasis. Overall, regional recurrence was observed in 2.8% of the necks (7/249): 1.6% (4/249) in dissected field and 1.2% (3/249) in undissected field. Seventy-eight percent (194/249) of the necks were staged pN0 with a subsequent failure rate of 1.5% (3/194); 16% (39/249) were staged pN1 and postoperative radiotherapy (PORT) was proposed in 21 of these patients. The failure rate with PORT was 9.5% and 5.5% without PORT. Six percent (16/249) of the necks were staged pN2b and all had PORT with one subsequent recurrence. Extracapsular spread (ECS) was reported in 16.5% of positive SND specimens (9/55); all by one were treated by PORT with a subsequent failure rate of 22% (2/9). At 3 years, overall survival for the whole population was 70% and statistically highly correlated with pN stage (p<0.001). These results support the reliability of SND to stage the clinically N0 neck. SND is a definitive operation not only in pN0 but also in most pN1 and pN2b necks. PORT is not justified in pN1 neck without ECS. In pN2b necks, the low rate of recurrence supports adjuvant PORT. The presence of ECS, despite adjuvant PORT, remains associated with a higher risk of recurrence.     

MTDH促进头颈鳞癌细胞放疗抵抗的实验研究

目的探讨星形胶质细胞上调基因1（astrocyte elevated gene 1,AEG 1,又称MTDH）对头颈部鳞状细胞癌（简称头颈鳞癌）放疗抵抗的影响。方法Western blotting检测放射线照射后头颈鳞癌细胞MTDH蛋白表达的改变。通过脂质体转染的MTDH cDNA和慢病毒介导的MTDH shRNA,分别在不同头颈鳞癌细胞中过表达和抑制MTDH,平板集落形成实验检测头颈鳞癌细胞放疗抵抗能力的改变,细胞免疫荧光染色检测DNA双链损伤指标γH2AX的表达。结果MTDH在头颈鳞癌细胞中的表达随着放射性照射剂量的增加和时间的延长逐渐升高。在CNE 2细胞中过表达MTDH,其体外集落形成能力增强;相反,在Tu686细胞中抑制MTDH的表达,其体外集落形成能力减弱。同时,细胞免疫荧光显示Tu686细胞在MTDH抑制后,其DNA双链损伤指标γH2AX的表达增加,表明DNA双链损伤修复过程受阻。结论MTDH能促进头颈鳞癌细胞放疗抵抗的形成,与其对DNA双链损伤修复的调控作用相关。     

Synchronous laryngeal squamous cell carcinoma and Hodgkin lymphoma of the head and neck region

During the pathologic examination of neck dissection specimens, unexpected findings may occasionally be encountered. Such findings include the presence of a second primary tumor or a chronic infectious or inflammatory disease. We report a case of a 65-year-old man who underwent a supracricoid partial laryngectomy and bilateral neck dissection for squamous cell carcinoma of the larynx. Histopathologic examination of the larynx revealed well-differentiated squamous cell carcinoma, but examination of the neck dissection specimen revealed a mixed cellularity subtype of classical Hodgkin lymphoma.     

Lymph node metastases from cutaneous squamous cell carcinoma of the head and neck

OBJECTIVE/HYPOTHESIS: Cutaneous squamous cell carcinoma (CSCC) has been reported to metastasize to parotid and cervical lymph nodes. Few prospective investigations of associated clinical and histopathologic findings and their effect on patient outcomes exist. We seek to identify risk factors for nodal metastases in CSCC and determine the impact of lymphatic spread on survival and recurrence. STUDY DESIGN: Subset analysis of a prospective, longitudinal database of patients with CSCC at a comprehensive cancer center. METHODS: Eligible patients with nonmelanoma skin cancer were consecutively enrolled in a prospective database from July 1996 through June 2001; this cohort was then followed to the key endpoints of recurrence and mortality. RESULTS: Two hundred ten patients were enrolled, and 193 patients with CSCC of the head and neck are included in this analysis. The incidence of nodal metastases in this population was 20.7% at study entry. Median follow-up was 20 months in patients with lymph node metastases and 24 months in patients without metastases. Nodal metastases were significantly associated with recurrent lesions (P = .002) and the following histopathologic features: lymphovascular invasion (P < .0001), inflammation (P = .010), poorly differentiated histology (P = .001), invasion into the subcutaneous tissues (P = .0001), perineural invasion (P = .005), and larger size (P = .0007). Metastases to the cervical nodes were not clinically apparent in 42% of patients with parotid metastases. Combination surgery and radiation therapy resulted in regional control rates of 95%, although local recurrence and distant metastases, along with second primary tumors, were the most frequent recurrent events. Kaplan-Meier survival analysis demonstrates a decrease in overall survival (P = .005), disease-free survival (P = .015), disease-specific survival (P = 0002), and time to recurrence (P = .012) in patients with nodal metastases compared with controls. CONCLUSIONS: Lymph node metastases from CSCC are common in our population and are associated with diminished survival. The presence of nodal spread occurs with other adverse histopathologic findings, and we recommend surgery and postoperative radiation therapy to control regional disease in the presence of nodal metastases and perineural invasion. New approaches in early identification of nodal metastases, treatment, and prevention of local recurrences and second primary malignancies are warranted.     

A matched survival analysis for squamous cell carcinoma of the head and neck in the elderly

OBJECTIVE: To determine whether elderly patients manifest poorer survivals for head and neck squamous cell carcinoma. METHODS: Cases of squamous cell carcinoma of the glottic larynx, oral tongue, and tonsil were extracted from the Surveillance, Epidemiology and End Results database for 1988 to 1998. For each primary site, patients were segregated into two age groups: 50 to 69 years of age and 70 years of age and older. For each case in the latter, elderly group, a reference group case was randomly matched for gender, year of diagnosis, cancer stage, extent of surgery, and radiation therapy. Overall survival and disease-specific survival were compared between the two groups with stage stratification with the Kaplan-Meier method. RESULTS: Cases of glottic carcinoma (1882), tongue carcinoma (426), and tonsillar carcinoma (200) in elderly patients were matched to the reference group. Overall mean survival differences were significant for glottic carcinoma (73.9 vs. 96.7 mo, elderly and younger groups, respectively) (P <.001) and tongue carcinoma (59.5 vs. 73.1 mo) ( P=.002) but not for tonsillar carcinoma (46.0 vs. 54.4 mo) ( P=.220). Disease-specific survival differences were significant but small in magnitude for glottic carcinoma (105.9 vs. 114.1 mo, respectively (P <.001) and tongue carcinoma (81.6 vs. 93.6 mo) (P =.009) but not for tonsillar carcinoma (71.5 vs. 70.7 mo) (P =.422). However, after stage stratification, elderly patients often did not exhibit statistically or practically significant poorer overall or disease-specific survivals. CONCLUSIONS: Elderly patients do not necessarily exhibit clinically significant poorer survivals for head and neck squamous cell carcinoma. Age alone should not be used to determine treatment options for elderly patients with squamous cell carcinoma.     

Selective neck dissection for the treatment of neck metastasis from squamous cell carcinoma of the head and neck

OBJECTIVE: Our objective was to determine the proportion of patients disease free in the neck, with the primary site controlled, who have been treated with a selective neck dissection (SND) for squamous cell carcinoma (SCCa) of the upper aerodigestive tract, and who had cervical metastasis less than 3 cm. STUDY DESIGN: A cohort of patients who fit the inclusion/exclusion criteria was identified retrospectively. Then all surviving patients were followed for a minimum of 2 years. METHODS: A group of 52 patients who had 58 selective neck dissections for cervical metastases from SCCa of the upper aerodigestive tract were identified. The mean age was 56 years (range, 20-85 y), there were 40 males and 12 females, and mean follow-up was 24.5 months (range, 1-64 mo). Twenty-six patients had clinically negative (cNo) neck examinations and 26 had clinically positive neck examinations. Postoperative radiation was given for extracapsular spread, greater than 2 positive nodes, T3, T4, or recurrent disease if the patient had not received radiation before surgery. These radiation criteria excluded 18 patients from postoperative radiation treatment. RESULTS: Kaplan-Meier survival analysis showed that the regional control rate with the primary site controlled was 0.94. Six patients developed recurrent neck disease. Three of these 6 patientswere surgically salvaged. Four recurrences were in the dissected field and 2 were out of the dissected field (level V). CONCLUSIONS: With similar indications for radiation therapy, the regional control rate in this cohort is comparable to control rates obtained with modified radical neck dissection.     

Basaloid squamous cell carcinoma of the head and neck

OBJECTIVE/HYPOTHESIS: Basaloid squamous cell carcinoma (BSCC), an uncommon tumor with predilection for the upper aerodigestive tract, is a distinct variant of squamous carcinoma, because of its unique histological features and ominous clinical behavior. This study reviews the experience in treating BSCC from two institutions. STUDY DESIGN: Retrospective. METHODS: H&E-stained sections from 20 patients with BSCC of the head and neck were reviewed and clinical follow-up was obtained for all patients. RESULTS: The study group consisted of 14 male and 6 female patients. Their ages ranged from 43 to 85 years, with a mean age of 62 years. Sites of origin included the larynx (4), tongue (3), pyriform sinus (3), nose (2), floor of mouth (2), mastoid (1), tonsil (1), epiglottis (1), nasopharynx (1), trachea (1), and palate (1). Pain was the most common presenting symptom (5 cases), followed by hoarseness and bleeding (3 cases each). Tobacco and alcohol abuse was noted in 17 patients. Treatment modalities included surgery with or without chemotherapy or radiotherapy in 13 patients, chemotherapy with irradiation in 2, chemotherapy alone in 2, and radiotherapy alone in 3. Clinical follow-up revealed no evidence of disease in 11 patients. Four were alive with disease at the time of writing and five died of disease. CONCLUSION: BSCC is a highly aggressive malignant tumor that presents in elderly patients who have a history of abuse of tobacco or alcohol, or both. Greater number of patients must be studied and compared with age-matched and stage-matched controls of conventional squamous cell carcinoma to determine whether the poor clinical outcome is related more to high-stage presentation or to the tumor's high-grade malignant cytological features.     

Prognostic factors for parotid metastasis of cutaneous squamous cell carcinoma of the head and neck

BackgroundCutaneous squamous cell carcinoma (CSCC) develops on the head in 80% of cases. Parotid metastasis (PM) is rare, but treatment, which associates surgery and radiation therapy, is heavy and prognosis poor.Material and methodsAll cases of parotidectomy for PM of CSCC of the head and neck between 2005 and 2015 were studied retrospectively. Epidemiologic, oncologic and therapeutic data were analyzed. Overall and specific survival were calculated following Kaplan-Meier. Log-rank and Cox models were used to identify prognostic factors for PM.ObjectivesThe principal study objective was to identify factors for survival in PM from CSCC of the head and neck.ResultsThirty-five patients were included. Mean time to onset of PM was 13 months. Overall 1-, 2- and 5-year survival was respectively 70, 66 and 59%. Independent prognostic factors comprised immunodepression, age at treatment, positive CSCC margins, macroscopic facial nerve involvement, and metastatic cervical adenopathies.ConclusionThe study confirmed an association of several independent prognostic factors at the stage of parotid lymph-node metastasis, related to patient, primary CSCC and PM. Complete primary resection is essential to reduce the risk of PM. Intensified radiologic and clinical surveillance should enable early diagnosis.