Cisplatin-based radiochemotherapy improves the negative prognosis of c-erbB-2 overexpressing advanced cervical cancer.

OBJECTIVES: To determine the impact of c-erb-B2 overexpression on disease-free survival (DFS) and local relapse in patients with advanced cervical cancer (CC) receiving concurrent chemoradiotherapy treatment. METHODS: A total of 136 patients with advanced CC (FIGO stage: IB2-IIA [12]; IIB [34]; IIIB [71]; IVA [19]; including both epidermoid [86] and adenocarcinoma [14]) were analyzed to determine c-erb-B2 levels by immunohistochemistry (c-erb-B2 antibody; Dako, Glostrup, Denmark). Only c-erb-B2+++ biopsies were considered positive. All patients received pelvic radiotherapy, brachytherapy, and concurrent chemotherapy with 2 different regimens: 48 patients were treated with tegafur (800 mg/d orally) and 88 with tegafur (same doses) plus 5 cycles of weekly cisplatin 40 mg/m/wk intravenously. RESULTS: A total of 32 (23.5%) biopsies were considered c-erb-B2-positive. Three-year and 5-year DFS were 61% and 58% for c-erb-B2-negative patients and 36% and 36% for c-erB2-positive patients, respectively (P = 0.02). Patients were stratified in 4 groups according to their c-erb-B2 status and whether they received cisplatin. The group of patients with c-erb-B2 overexpression that did not receive platinum treatment had a higher rate of pelvic relapse (P < 0.0001), associated with a decreased DFS (P = 0.0014). CONCLUSIONS: c-erb-B2 overexpression may imply a poor prognosis for patients with advanced CC. Treatment with cisplatin-based radiochemotherapy improved outcome in these patients.

Negative prognostic impact of the coexpression of epidermal growth factor receptor and c-erbB-2 in locally advanced cervical cancer.

OBJECTIVE: The objective was to determine the impact of the coexpression of epidermal growth factor receptor (EGFR) and tumor marker c-erbB-2 on disease-free survival (DFS) and pelvic relapse-free survival (PRFS) in patients with locally advanced cervical cancer (LACC) receiving concurrent chemoradiotherapy. METHODS: The expression of EGFR and c-erbB-2 was assessed by immunohistochemistry, which was centralized and blinded to outcome. Univariate and multivariate analyses were used to evaluate the impact of EGFR and c-erbB-2 on DFS and PRFS. RESULTS: 170 patients with LACC were included and received concurrent chemoradiotherapy. 25 (15%) biopsies were considered EGFR and c-erbB-2 positive; 100 (59%) were either EGFR or c-erbB-2 positive, and 45 (26%) were EGFR and c-erbB-2 negative. The 3- and 5-year DFS was 39% each for EGFR- and c-erbB-2-positive patients, 54 and 49%, respectively, for EGFR- or c-erbB-2-positive patients, and 76 and 72%, respectively, for EGFR- and c-erbB-2-negative patients (p = 0.006). EGFR- and c-erbB-2-positive tumors were significantly associated with a decrease in PRFS (hazard ratio, HR, 3.99; 95% confidence interval, CI, 1.44-11.05, p = 0.007), and DFS (HR 2.9; 95% CI, 1.26-6.66, p = 0.01). CONCLUSION: Patients with LACC coexpressing EGFR and c-erbB-2, and treated with concurrent chemoradiotherapy, had a worse clinical prognosis with shorter DFS and PRFS.

Loss of the mitochondrial bioenergetic capacity underlies the glucose avidity of carcinomas.

The down-regulation of the catalytic subunit of the mitochondrial H+-ATP synthase (beta-F1-ATPase) is a hallmark of most human carcinomas. This characteristic of the cancer cell provides a proteomic signature of cellular bioenergetics that can predict the prognosis of colon, lung, and breast cancer patients. Here we show that the in vivo tumor glucose uptake of lung carcinomas, as assessed by positron emission tomography in 110 patients using 2-deoxy-2-[18F]fluoro-d-glucose as probe, inversely correlates with the bioenergetic signature determined by immunohistochemical analysis in tumor surgical specimens. Further, we show that inhibition of the activity of oxidative phosphorylation by incubation of cancer cells with oligomycin triggers a rapid increase in their rates of aerobic glycolysis. Moreover, we show that the cellular expression level of the beta-F1-ATPase protein of mitochondrial oxidative phosphorylation inversely correlates (P < 0.001) with the rates of aerobic glycolysis in cancer cells. The results highlight the relevance of the alteration of the bioenergetic function of mitochondria for glucose capture and consumption by aerobic glycolysis in carcinomas.

Susceptibility of pRb-deficient epidermis to chemical skin carcinogenesis is dependent on the p107 allele dosage.

Functional inactivation of the pRb-dependent pathway is a general feature of human cancer. However, only a reduced spectrum of tumors displays inactivation of the Rb gene. This can be attributed, at least partially, to the possible overlapping functions carried out by the related retinoblastoma family members p107 and p130. We observed that loss of pRb in epidermis, using the Cre/LoxP technology, results in proliferation and differentiation defects. These alterations are partially compensated by the elevation in the levels of p107. Moreover, epidermis lacking pRb and p107, but not pRb alone, develops spontaneous tumors, and double deficient primary keratinocytes are highly susceptible to Ha-ras-induced transformation. Two-stage chemical carcinogenesis experiments in mice lacking pRb in epidermis revealed a reduced susceptibility in papilloma formation and an increase in the malignant conversion. We have now explored whether the loss of one p107 allele, inducing a decrease in the levels of p107 up to normal levels could restore the susceptibility of pRb-deficient skin to two-stage protocol. We observed partial restoration in the incidence, number, and size of tumors. However, there is no increased malignancy despite sustained p53 activation. We also observed a partial reduction in the levels of proapoptotic proteins in benign papillomas. These data confirm our previous suggestions on the role of p107 as a tumor suppressor in epidermis in the absence of pRb.

Overexpression of PIK3CA in head and neck squamous cell carcinoma is associated with poor outcome and activation of the YAP pathway.

OBJECTIVES: Phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) is commonly altered in many human tumors, leading to the activation of p110α enzymatic activity that stimulates growth factor-independent cell growth. PIK3CA alterations such as mutation, gene amplification and overexpression are common in head and neck squamous cell carcinoma (HNSCC) and. We aim to explore how these alterations and clinical outcome are associated, as well as the molecular mechanisms involved. MATERIAL AND METHODS: Mutation and copy-number variation in PIK3CA, and whole-genome expression profiles, were analyzed in primary HNSCC tumors from The Cancer Genome Atlas (TCGA) cohort (n = 243). The results were validated in an independent cohort form the University Hospital of A Coruña (UHAC, n = 62). Expression of the PIK3CA gene protein product (PI3K p110α) and nuclear YAP were assessed in tissue microarrays in a cohort from the University Hospital 12 de Octubre (UH12O, n = 91). RESULTS: Only high expression of the PIK3CA gene was associated with poor clinical outcome. The study of gene expression, transcription factor and protein signatures suggested that the activation of the Hippo-YAP pathway, involved in organ size, stem cell maintenance and tumorigenesis, could underlie tumor progression in PI3KCA overexpressing tumors. Tissue arrays showed that PI3K p110α levels correlated with YAP nuclear localization in HNSCC tumors. CONCLUSIONS: High expression of PIK3CA in HNSCC primary tumors identifies patients at high risk for recurrence. In these tumors, progression could rely on the Hippo-YAP pathway instead of the canonical Akt/mTOR pathway. This observation could have important implications in the therapeutic options for patients.

Prognostic value of KIT expression in small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) is a very aggressive disease, with poor survival rates despite standard treatment with combination chemotherapy with or without radiotherapy. Further insights into the molecular biology of this malignant tumour are needed to improve the therapeutic approaches and outcome. KIT protein is expressed in SCLC, and its kinase activity has been implicated in the pathophysiology of many tumours, including SCLC. The purpose of this study was to evaluate the prevalence of KIT expression in patients with SCLC and its prognostic value. METHODS: We performed an inmunohistochemical analysis of 204 SCLC samples to determine KIT protein expression. The relationship between KIT expression and clinicopathological parameters was evaluated. Univariate and multivariate analyses were performed to define its prognostic significance. RESULTS: KIT expression was observed in 149 of 204 tumour tissues (73%). KIT expression was associated with advanced disease and with decreased incidence of bone metastases. No significant differences were observed for time to disease progression (TTP) (9.1% versus 6.2% at 3 years, p=0.6) or overall survival (OS) (10.7% versus 6.9% at 3 years, p=0.37) among patients with KIT positive versus negative tumours, respectively. Multivariate analysis showed that sex, tumour stage, albumin levels and response to therapy were the only independent predictors for survival. CONCLUSION: KIT protein is expressed in a high percentage of SCLC tumours. In our study population, however, the expression of KIT had no significant impact on survival.

Myxoinflammatory fibroblastic sarcoma: report of a case with fine needle aspiration cytology.

BACKGROUND: Myxoinflammatory fibroblastic sarcoma (MFS) is a distinct neoplasm that usually arises in the acral zones of distalextremities. We report, for the first time, the preoperative fine needle a,spiration cytology (FNAC) findings of an MFS case that was confirmed after surgical excision. CASE: An 81-year-old woman presented with a multinodular tumor in the distal right extremity that had been present for 1 year. FNA C of the lesion was performed and followed by local excision. The fine needle aspiration smears contained 2 of the 3 types of neoplastic cells that have been observed in MFS: spindled and ganglionlike cells. The background was myxoid, with a prominent inflammatory infiltrate. Histopathologic examination of the surgical specimen confirmed the diagnosis of MFS. CONCLUSION: Although the cytologic diagnosis was "pleomorphic sarcoma," MFS was considered and local excision recommended, given the reported low grade nature of this entity. However, the need for extreme caution in the diagnosis of soft tissue lesions on cytologic grounds alone cannot be overemphasized.

Primary papillary serous carcinoma of the peritoneum: report of a case with diagnosis by fine needle aspiration and immunocytochemistry.

BACKGROUND: Primary papillary serous carcinoma (PPSC) of the peritoneum is a rare neoplasm, histologically indistinguishable from papillary serous carcinoma of the ovary, which diffusely involves the peritoneum but spares or minimally invades the ovaries. To the best of our knowledge, the preoperative and the fine needle aspiration diagnosis of this disorder have not been reported before. CASE: A woman developed an extensive peritoneal neoplasm 4 years after hysterectomy and bilateral salpingo-oophorectomy for benign disease. Fine needle aspiration of the tumor was performed, and the cytologic and immunocytochemical findings were consistent with papillary serous carcinoma. A diagnosis of PPSC of the peritoneum was rendered because review of all slides from previous surgical specimens showed no evidence of carcinoma and no other primary tumors were found elsewhere. CONCLUSION: Fine needle aspiration cytology coupled with immunocytochemical and clinical data allows an unequivocal preoperative diagnosis of papillary serous carcinoma (primary peritoneal or with an ovarian origin). The sole limitation to establish a primary peritoneal origin before surgery is the requirement to histologically study the ovaries. Based on this fact, the preoperative fine needle aspiration cytology diagnosis of PSCP should be restricted to oophorectomized patients.

Unexpected roles for pRb in mouse skin carcinogenesis.

The mouse skin carcinogenesis represents one of the best models for the understanding of malignant transformation, including the multistage nature of tumor development. The retinoblastoma gene product (pRb) plays a critical role in cell cycle regulation, differentiation, and inhibition of oncogenic transformation. In epidermis, Rb-/- deletion leads to proliferation and differentiation defects. Numerous evidences showed the involvement of the retinoblastoma pathway in this model. However, the actual role of pRb is still unknown. To study the possible involvement of pRb in keratinocyte malignant transformation, we have carried out two-stage chemical skin carcinogenesis on Rb(F19/F19) (thereafter Rb+/+) and Rb(F19/F19);K14Cre (thereafter Rb-/-) animals. Unexpectedly, we found that Rb-/- mice developed fewer and smaller papillomas than the Rb+/+ counterparts. Moreover, the small size of the pRb-deficient tumors is associated with an increase in the apoptotic index. Despite this, pRb-deficient tumors display an increased conversion rate to squamous cell carcinomas. Biochemical analyses revealed that these characteristics correlate with the differential expression and activity of different pathways, including E2F/p19arf/p53, PTEN/Akt, c-jun NH2-terminal kinase/p38, and nuclear factor-kappaB. Collectively, our findings show unexpected and hitherto nondescribed roles of pRb during the process of epidermal carcinogenesis.

DEK oncogene is overexpressed during melanoma progression.

DEK is an oncoprotein involved in a variety of cellular functions, such as DNA repair, replication, and transcriptional control. DEK is preferentially expressed in actively proliferating and malignant cells, including melanoma cell lines in which DEK was previously demonstrated to play a critical role in proliferation and chemoresistance. Still, the impact of this protein in melanoma progression remains unclear. Thus, we performed a comprehensive analysis of DEK expression in different melanocytic tumors. The immunostaining results of 303 tumors demonstrated negligible DEK expression in benign lesions. Conversely, malignant lesions, particularly in metastatic cases, were largely positive for DEK expression, which was partially associated with genomic amplification. Importantly, DEK overexpression was correlated with histological features of aggressiveness in primary tumors and poor prognosis in melanoma patients. In conclusion, our study provides new insight into the involvement of DEK in melanoma progression, as well as proof of concept for its potential application as a marker and therapeutic target of melanoma.

Prognostic value of the epidermal growth factor receptor (EGRF) and p53 in advanced head and neck squamous cell carcinoma patients treated with induction chemotherapy.

We measured the expression of the p53 nuclear protein and epidermal growth factor receptor (EGFR) in 46 biopsy samples from patients with advanced head and neck cancer treated with induction combination chemotherapy of 5-fluorouracil, cisplatin, and paclitaxel. Tumour expression of p53 protein was analysed with the monoclonal D07 antibody and EGFR with monoclonal H11 antibody. The overall response, defined as complete (CR) and partial response (PR) rates to treatment, was 88%. p53 positive staining was significantly more frequent in patients who did not respond to the induction treatment. EGFR expression failed to show any correlation with the response rate. Multivariate analysis indicated that a tumour location in the oral cavity together with p53 expression combined with moderate-to-high EGFR staining were independent prognostic factors of a shorter disease-free survival (DFS). Location of the tumour in the oral cavity and EGFR expression had independent prognostic value for overall survival (OS). We conclude that the EGFR status and an oral cavity location of the tumour have independent prognostic value in patients with advanced head and neck carcinoma treated with induction chemotherapy. The p53 status appears to be a determinant of the tumour chemo-sensitivity in advanced head and neck squamous cell carcinoma (HNSCC). The presence in the tumour of a p53-positive stain and moderate-to-high staining of EGFR is associated with a shorter DFS and time to treatment failure (TTF) probably reflecting a more aggressive tumour phenotype.

Cyclin A as a predictive factor for chemotherapy response in advanced head and neck cancer.

PURPOSE: Overall survival of head and neck squamous cell cancer (HNSCC) patients has not improved despite advances in our understanding of the biology and molecular features of this disease. In particular, patients with advanced HNSCC have the poorest prognosis. To understand more about the contribution of cell cycle alterations to HNSCC development and their possible value in predicting prognosis and response to chemotherapy, we evaluated the levels of proteins involved in cell cycle control in patients diagnosed with advanced HNSCC. EXPERIMENTAL DESIGN: A tissue microarray was made with 122 HNSCC specimens obtained from biopsy material. Protein expression was evaluated by immunohistochemistry and correlated with clinical and pathological characteristics. RESULTS: Multiple alterations at various checkpoints of cell cycle progression were observed. Loss of P16 protein was less common in oropharyngeal tumors than at other HNSCC locations (P = 0.02). Evaluation of the simultaneous expression of different proteins highlighted direct correlations (P < 0.05) such as that of the cyclin-dependent kinases with their cyclin-partners, and the Ki-67 protein with cyclin-dependent kinases 1, cyclin A (CA) and cyclin B1. Median overall survival and time-to-progression were longer in patients with CA-expressing tumors (not reached versus 34.4 months, P = 0.02) and (47.3 versus 14.6 months, P = 0.006), respectively. Moreover, expression of CA in tumors predicted a better response to chemotherapy. Positive expression of cyclin E in tumors was also associated with an increased median time-to-progression (14.6 versus 25.8 months, P = 0.04). Finally, patients with cyclin D1-expressing tumors had shorter median overall survival (29.6 months versus not reached, P = 0.05) and shorter median time-to-progression (21.5 months versus not reached, P = 0.06). However, in a multivariate analysis a CA-negative-expressing tumor was the only independent poor prognostic factor in the entire cohort of HNSCC patients [odds ratio, 2.3; 95% confidence interval (CI) = 1.2-4.5; P = 0.01]. CONCLUSIONS: Our results provide detailed information on the molecular profile of cell cycle components in HNSCCs and identify CA-negative-expressing tumors as an independent marker of tumor progression and poor response to chemotherapy in patients diagnosed with advanced HNSCC.

Dedifferentiated liposarcoma of the pyriform sinus: report of a case and review of the literature.

Laryngeal and hypopharyngeal liposarcomas are extraordinarily infrequent tumors. To the best of our knowledge there are fewer than 40 well-documented cases reported to date. Almost all of them are well-differentiated liposarcomas, with only 2 laryngeal-hypopharyngeal dedifferentiated liposarcomas. Dedifferentiated liposarcoma is defined as a well-differentiated liposarcoma with areas of high-grade spindle cell nonlipogenic sarcoma. The well-differentiated areas may be of a lipoma-like, sclerosing, or mixed type, and the dedifferentiated areas most frequently are of malignant fibrous hystiocytoma-like type. Despite its commonly pleomorphic histology, dedifferentiated liposarcoma does not behave as aggressively as most pleomorphic sarcomas of adulthood; however, it has the capacity to metastasize, in contrast to its well-differentiated counterpart. We present a case of dedifferentiated liposarcoma arising in the pyriform sinus, an event only twice reported previously in the literature.

Paratesticular congenital malignant rhabdoid tumor diagnosed by fine-needle aspiration cytology. a case report.

We report the FNA features of a congenital malignant extrarenal rhabdoid tumor (MERT) located in the right paratesticular area of a newborn full-term boy (39 wk gestation), with disseminated metastases in the liver and right parietal region. The diagnosis was suggested two days after birth by fine-needle aspiration biopsy (FNAB) of the parietal mass, which demonstrated an atypical large cell proliferation with vesicular nuclei, prominent nucleoli, and abundant cytoplasm exhibiting paranuclear dense inclusions. The diagnosis was confirmed by histopathologic and immunohistochemical examination of the primary paratesticular tumor. To the best of our knowledge, this is the third MERT reported in the paratesticular region, one of the few congenital extrarenal non-central nervous system cases, and the third congenital case (renal or extrarenal) primarily diagnosed by FNAB. We emphasize the characteristic cytologic features of a congenital rhabdoid tumor, which must be known by pathologists because of the clinical and prognostic implications. Diagn. Cytopathol. 2004;30:46-50.

Marginal zone B-cell lymphoma of the parotid gland associated with epithelioid granulomas. Report of a case with fine needle aspiration.

BACKGROUND: Although granulomas can occur in association with malignant neoplasms, including some subtypes of lymphoma, they have been described rarely in marginal zone B-cell lymphoma (MZCL). To our knowledge, the cytologic features of this association have not been documented. We present the cytologic findings with fine needle aspiration cytology (FNAC) of an unusual case of MZCL with concomitant granulomas. CASE: An 82-year-old male presented with a mass in the left parotid gland. The lesion was evaluated by FNAC. The smears showed syncytial aggregates of epithelioid histiocytes intermixed with small and medium-sized lymphoid cells containing round to irregular-shaped nuclei and small nucleoli. Some of these cells had a greater amount of cytoplasm and frequently had a plasmacytoid appearance. The lesion was removed, and histopathologic study showed MZCL associated with extensive nonnecrotizing granulomas. CONCLUSION: Granulomatous reactions can be seen in rare cases of MZCL. However, the cytologic features of the lymphoid infiltrate can suggest the possibility of MZCL in the clinical setting of FNAC performed from an extranodal location, such as the parotid gland.

Fine needle aspiration cytology of clear cell carcinoma of the gallbladder with hepatic infiltration: a case report.

BACKGROUND: Clear cell carcinoma of the gallbladder (CCG) is an unusual histologic variant recognized in the World Health Organ ization classification of tumors of the gallbladder and extrahepatic bile ducts. Although the clinicopathologic features have been documented in a few reports, to our knowledge the cytologic findings have not been described before. We report the fine needle aspiration cytology (FNAC) findings in a case of CCG with hepatic infiltration. CASE: A 72-year-old woman presented with right upper quadrant pain and hepatomegaly. Serum levels of CA19-9 and alpha-fetoprotein were elevated. Computed tomography revealed several hepatic nodules, the larger of which was a mass in contact with the gallbladder, which had a thickened wall. FNAC showed loose sheets and disassociated cells with abundant, clear, finely vacuolated cytoplasm. Atypical bare nuclei, binucleated cells and some multinucleated cells were also found. A simultaneous trucut biopsy from the main hepatic mass confirmed the diagnosis. CONCLUSION: CCG is a clear cell neoplasm that should be considered when clear changes are observed on FNAC. Recognition of the cytologic features, together with adequate clinicoradiologic study, may be sufficient to establish the diagnosis.

Incidence of human papillomavirus-related oropharyngeal cancer and outcomes after chemoradiation in a population of heavy smokers.

BACKGROUND: Incidence of human papillomavirus (HPV)-related oropharyngeal carcinomas is increasing worldwide. The purpose of this study was to report the incidence in our region, and to determine the influence of HPV status on survival among a heavy smoking population. METHODS: p16 expression was analyzed in 102 patients with stage II to IV treated with chemoradiation. Overall survival (OS), locoregional control, and disease-free survival (DFS) were compared for HPV+ and HPV- status. RESULTS: The majority of patients were smokers (86%). p16 positivity was found in 26.7%. Patients who were HPV+ were younger (56 vs 59 years old; p = .052). No differences were observed regarding tumor stage, sex, or smoking between HPV+ and HPV-. Three-year OS was 67.4% for patients who were HPV+ versus 49.7% for HPV- (hazard ratio [HR], 0.55; p = .095). CONCLUSION: Incidence of HPV-related oropharyngeal carcinoma in Spain is similar to that reported in other European countries. In this sample of heavy smokers, we observed a nonsignificant trend for better outcomes in patients who were HPV+.

Biological markers of cisplatin resistance in advanced testicular germ cell tumours.

INTRODUCTION: Germ cell tumours (GCTs) of the testis show exquisite sensitivity to treatment with cisplatin. Despite the high cure rates provided by platinum-based chemotherapy, 10-20% of patients die from progressive disease. Although various cellular pathways may influence cisplatin efficacy, their actual impact has not been comprehensively investigated in advanced GCTs. The objective of the present study was to clarify the role of the expression status of proteins involved in the Rb and p53 tumour suppressor pathways in sensitivity and resistance of GCTs to cisplatin-based chemotherapy. MATERIALS AND METHODS: Paraffin-embedded tumour tissues from 84 patients with advanced GCT treated with cisplatin-based chemotherapy were analysed. Immunohistochemical expression of proteins p53 and mdm2, and the G1-phase cyclins D1 and D2 (CD1 and CD2) was assessed and correlated with the clinical course. RESULTS: The percentages of positive expression of p53, mdm2, CD1 and CD2 were 56, 57, 37.5 and 55%, respectively. From univariate analysis, there was no significant association between p53, mdm2 or CD1 expression and outcome. Instead, positive CD2 expression was found to be marginally associated with shorter median duration of progression-free survival (PFS) (p=0.06). In multivariate analysis, none of the molecular markers retained statistical significance with treatment response or survival. CONCLUSIONS: Tissular expression of p53, mdm2 and CD1 is not associated with prognosis or treatment response in patients with advanced GCT. Aberrant CD2 expression appears to further determine a shorter PFS. Larger and further studies are required to validate CD2 as a marker of cisplatin resistance.

Impact of epidermal growth factor receptor expression on disease-free survival and rate of pelvic relapse in patients with advanced cancer of the cervix treated with chemoradiotherapy.

OBJECTIVES: To determine the impact of the expression of epidermal growth factor receptor (EGFR) on disease-free survival (DFS) and on pelvic relapse in patients with advanced cancer of the cervix receiving concurrent chemoradiotherapy. METHODS: In 112 consecutive patients with advanced cancer of the cervix (11 stage IB2-IIA, 25 IIB, 63 IIIB, 13 IVA) treated with chemoradiotherapy between December 1994 and September 2004, the expression of EGFR using histoimmunochemistry was measured and used in univariate and multivariate analysis, along with variables such as age, International Federation of Gynecology and Obstetrics Staging System for Epithelial Ovarian Cancer (FIGO) stage, histology, Eastern Cooperative Oncology Group (ECOG), tumor size, and ganglia involvement diagnosed with computerized axial tomography, treatment with cisplatin to evaluate its impact on DFS and pelvic relapse. RESULTS: Of the 112 biopsies, 32 (28.6%) were negative or slightly positive (EGFR±) and 80 (71.4%) were moderate or intensely positive (EGFR++/+++). The overexpression of EGFR (++/+++) was significantly associated with an epidermoid histology (P < 0.0001), with a higher rate of pelvis relapse and a decreased DFS (hazard ratio [HR]: 2.31 [1.08-4.96]; P = 0.03). Overall, treatment with cisplatin increased DFS (HR: 0.51 [0.26-0.97]; P = 0.04). CONCLUSIONS: Patients with tumors of the cervix and overexpression of the EGFR++/+++ show a higher probability of pelvic relapses and a decreased disease-free survival. The poor prognosis of these tumors may be a consequence of an increase in radio-resistance.

Expression of EGFR, HER-2/neu and KIT in germ cell tumours.

BACKGROUND: Germ cell tumours (GCTs) represent an extraordinarily chemosensitive malignancy. However, 20-30% of patients with advanced disease cannot be cured by currently available treatments. The role of tyrosine kinase receptors has been widely studied in other malignancies. Yet, limited information is available on GCTs. METHODS: One hundred and nine paraffin-embedded GCTs in 84 patients were assessed by immunohistochemistry for epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER-2)/neu and KIT (CD117) expression. Univariate and multivariate analyses were performed to evaluate their role as predictive and/or prognostic factors. RESULTS: EGFR and HER-2/neu staining was detected in 28% and 13% of tumours, respectively, predominantly in nonseminomatous GCTs. KIT protein was almost universally expressed in seminomas (97%), being virtually absent in choriocarcinoma and teratocarcinoma subtypes. EGFR expression showed inverse association with tumour response of borderline significance. With a median follow-up of 10.6 years, no significant association was observed between the expression of any of these markers and relapse-free or overall survival. CONCLUSIONS: EGFR, HER-2/neu and KIT have differential patterns of expression in GCTs according to histological subtypes. The expression of these markers in our series had no prognostic or predictive significance.