MAGE-A and NY-ESO-1 expression in cervical cancer: prognostic factors and effects of chemotherapy.

OBJECTIVE: The aim of this study was to evaluate the prevalence of cancer testis tumor-associated antigens MAGE-A and NY-ESO-1 in cervical cancer and correlate expression patterns with clinicopathologic parameters and prognosis. STUDY DESIGN: One hundred sixty-two cervical cancer samples from 109 patients who were treated with radical hysterectomy, neoadjuvant chemotherapy, or pelvic disease recurrence were analyzed by immunohistochemistry. RESULTS: MAGE-A was expressed by 32/94 (34%) and 7/15 (47%) previously untreated and recurrent tumors, respectively. NY-ESO-1 was expressed by 46/94 (49%) and 6/15 (40%) previously untreated and recurrent tumors, respectively. MAGE-A in early stage tumors was correlated to tumor size and lymph node metastases (P = .024 and P = .046, respectively) whereas NY-ESO-1 to tumor grading (P = .039). CONCLUSION: Cervical cancer frequently expresses cancer testis tumor-associated antigens. MAGE-A and NY-ESO-1 expression rates are not influenced by systemic therapies. Cancer testis tumor-associated antigens are correlated to common prognostic factors.

Cancer testis antigen expression in primary and recurrent vulvar cancer: association with prognostic factors.

Cancer testis tumour associated antigens (C/T-TAAs) were investigated in several gynaecologic and non-gynaecologic neoplasms as possible prognostic markers and targets for immunotherapy. The objective of the present study was to evaluate C/T-TAA expression patterns and prognostic significance in patients affected by vulvar cancer. Melanoma antigen E (MAGE)-A1, MAGE-A4 and NY-ESO-1 expression was determined by immunohistochemistry in paraffin-embedded tissue specimens from 45 primary and 14 recurrent vulvar carcinomas treated with surgery. MAGE-A1, MAGE-A4 and NY-ESO-1 were expressed in 25 (42%), 38 (64%) and 40 (68%) of the 59 samples, respectively. MAGE-A4 was significantly more frequently expressed in tumours with lymph node metastases (p<0.002) and in recurrent tumours (p<0.02). NY-ESO-1 was more highly expressed by moderately or poorly differentiated tumours (p<0.01). This study demonstrates that vulvar cancer frequently expresses C/T-TAAs. Antigen expression correlates with the presence of lymph node metastases and poor tumour differentiation.

Rosai-Dorfman disease: two case reports and diagnostic role of fine-needle aspiration cytology.

Rosai-Dorfman disease, or sinus histiocytosis with massive lymphadenopathy (SHML), is a rare and self-limiting benign disorder that most commonly involves the cervical lymph nodes. The authors describe two cases of SHML. Fine-needle aspiration of the lymphadenopathy was performed in both patients. Immunocytochemical and histologic features, as the evidence of emperipolesis and S100 protein positivity on immunostaining, were typical of SHML. Fine-needle aspiration cytology plays an important diagnostic role in SHML and may be conclusive in a typical clinical setting. The diagnosis of SHML should be considered in the differential diagnosis of massive, painless cervical lymphadenopathy. Long-term follow-up is necessary to observe the complete regression of the massive lymphadenopathy. However, specific therapy is available and should be limited to patients with compressive symptoms or extranodal disease.

Expression of the CDK inhibitor p27kip1 and oxidative DNA damage in non-neoplastic and neoplastic vulvar epithelial lesions.

Vulvar cancer represents an important medical problem worldwide whose incidence is increasing at an alarming rate in young females. Several factors have been linked to vulvar cancer development, but its exact pathogenesis remains to be determined. Vulvar tumorigenesis proceeds through intermediate dysplastic lesions, known as vulvar intraepithelial neoplasias, frequently associated with non-neoplastic epithelial disorders of the vulva, such as lichen sclerosus and squamous cell hyperplasia. In this study, the expression of the CDK inhibitor p27Kip1 and the extent of endogenous oxidative DNA damage were evaluated in vulvar specimens, including normal tissues, lichen sclerosus, squamous cell hyperplasia, vulvar intraepithelial neoplasias and invasive squamous cell carcinomas. We found that p27Kip1 was constantly expressed in normal vulvar epithelium cells while a progressive significant reduction in the percentage of p27Kip1-positive cells was observed in vulvar intraepithelial neoplasias (77%) and in invasive carcinomas (64%). Mean percentage of positive cells in invasive carcinomas, but not in vulvar intraepithelial neoplasias, was also significantly lower than squamous cell hyperplasia lesions (78%) while lichen sclerosus displayed a percentage of positive cells (45%) significantly lower than both vulvar intraepithelial neoplasias and invasive carcinomas. 8-hydroxydeoxyguanosine (8-OHdG) is considered a sensitive biomarker for oxidative stress. We observed a progressive significant increase in the levels of 8-OHdG and in the percentage of positive cells from normal vulvar epithelium to vulvar intraepithelial neoplasias (25%) and to invasive carcinomas (64%). Squamous cell hyperplasia displayed an intermediate percentage of positive cells comparable to vulvar intraepithelial neoplasias 2 but significantly higher than vulvar intraepithelial neoplasias 1 and lower than invasive carcinomas. Lichen sclerosus staining was significantly lower than carcinomas but higher than vulvar intraepithelial neoplasias and squamous cell hyperplasia. These results demonstrate that expression of p27Kip1 is downregulated while oxidative DNA damage increases from early non-neoplastic epithelial alterations through vulvar intraepithelial neoplasias to invasive vulvar carcinomas. Thus, both parameters might play an important role in the development of this cancer and their study might contribute to our understanding of human vulvar carcinogenesis.

Aberrant expression of alpha-dystroglycan in cervical and vulvar cancer.

OBJECTIVES: Cervical and vulvar cancers develop through well-defined precursor lesions but their exact pathogenesis is still unknown. The dystroglycan complex is a transmembrane glycoprotein that forms a continuous link from the extracellular matrix to the actin cytoskeleton. Deregulated expression of dystroglycan has been reported in human malignancies and related to tumor differentiation and aggressiveness. In this study, expression of dystroglycan was evaluated in the multistep cervical and vulvar tumorigenesis. METHODS: Expression of the dystroglycan complex was evaluated by immunostaining in lesions representing different stages of vulvar and cervical tumorigenesis using a monoclonal antibody which recognizes carbohydratic epitopes on the alpha-dystroglycan subunit. RESULTS: alpha-dystroglycan was constantly detected in normal cervical epithelium with a mean percentage of positive cells higher than 80%. A progressive significant reduction in the mean percentage of positive cells was observed in low (67%) and high grade SIL (14%) and in invasive carcinomas (2.6%) of the cervix. In cancers, no differences were observed in terms of percentage of positive cells when cases were stratified according with either tumor grade or stage. A progressive significant reduction in the mean percentage of positive cells was also observed from normal vulvar epithelium (90%) to VIN1 (66%), VIN2 (28%) and invasive vulvar carcinomas (22%). No significant decrease in the alpha-dystroglycan staining was observed in squamous cell hyperplasia lesions (85%) while lichen sclerosus displayed a percentage of positive cells (47%) significantly lower than normal epithelium. CONCLUSIONS: Detection of alpha-dystroglycan is frequently lost in human cervical and vulvar tumorigenesis and further studies are warranted to verify whether evaluation of this molecule might serve as marker of risk progression of preneoplastic lesions and to better understand its significance in terms of cancer development.

Chordoma of the low cervical spine presenting with Horner's syndrome.

Chordomas arising from the low cervical spine have been reported rarely. This case report expands the knowledge of chordomas of the low cervical spine by reporting the clinical, radiological, and pathological findings of a case of chordoma arising from C6 vertebra in a 61-year-old man presenting with left Horner's syndrome. This clinical presentation is uncommon for cervical chordomas and resulted from the tumor growth in the left carotid space resulting in the total encasement of common carotid artery and involvement of sympathetic fibers ipsilaterally.

Pseudo-Meigs' syndrome associated with malignant struma ovarii: a case report.

BACKGROUND: Malignant struma ovarii is a rare tumor, consisting of a struma ovarii with malignant transformation. The association of a malignant struma ovarii with pseudo-Meigs' syndrome and elevated Ca-125 levels has been never reported. CASE: A 66-year-old woman presented with monolateral ovarian mass, ascites, hydrothorax, and elevated Ca-125 levels. Optimal medical staging was performed. Definitive histological examination revealed a malignant struma ovarii. The immediate and complete resolution of symptoms and rapid decline of both Ca-125 and thyroglobulin levels to normal value were achieved post-operatively. After counseling, strict follow-up was planned, and no adjuvant therapy was administered. CONCLUSION: We report the first case of pseudo-Meigs' syndrome associated with malignant struma ovarii and elevated Ca-125 levels. The choice of not performing adjuvant therapy is feasible after optimal surgery and adequate staging procedure given to the usually clinical benign course and the low incidence of metastases in malignant struma ovarii. Careful patient counseling is required.

Decreased expression of the CDK inhibitor p27Kip1 and increased oxidative DNA damage in the multistep process of cervical carcinogenesis.

OBJECTIVE: The expression of the CDK inhibitor p27Kip1 and the extent of endogenous oxidative DNA damage were evaluated in the multistep cervical carcinogenesis. METHODS: Archival specimens of low-grade (L) squamous intraepithelial lesions (SILs) (n=32), high-grade (H) SILs (n=24) and invasive carcinomas (n=48) of the cervix were included in the analysis compared with normal cervical squamous epithelium (n=15). Expression level of p27Kip1 was evaluated by immunostaining. Immunohistochemical detection of 8-hydroxydeoxyguanosine (8-OHdG) was considered as marker of oxidative DNA damage in the same tissues. RESULTS: p27Kip1 was constantly expressed in normal epithelium with a mean percentage of positive cells higher than 50%. A progressive significant reduction in the mean percentage of positive cells was observed in L-SIL (18.1%), H-SIL (7.3%) and in invasive carcinomas (2.5%). A progressive significant increase in the levels of 8-OHdG and in the percentage of mean positive cells was observed from L-SIL (2.2%) to H-SIL (12.5%) to invasive carcinomas (25.2%). p27Kip1 and 8-OHdG expression displayed a significant inverse relationship. CONCLUSIONS: Expression of p27Kip1 is down-regulated while oxidative DNA damage increases during cervical carcinogenesis. Both parameters are altered at early stages of the process and might help to predict patients at high risk of progression.