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ABSTRACT: Treatment of patients with vulvar cancer is challenging for gynaecologic oncologists. Owing to the localization in a sensitive area, surgical radicality and the indication for adjuvant treatment have to be balanced with psychosocial aspects to treat patients adequately. Clinical management is therefore highly dependent on the tumour stage. For patients with early-stage disease (FIGO I-II) therapy mainly concentrates on surgery with resection of the primary tumour and staging of the groin lymph nodes. In intermediate-stage vulvar cancer (FIGO III), advanced disease is expressed by affected inguinofemoral lymph nodes bringing radical lymphadenectomy and adjuvant therapy as well as radiation or chemoradiation into the focus of treatment. For locally advanced or metastatic vulvar cancer (FIGO IV) neoadjuvant or definitive chemoradiation has to be considered besides surgery. Owing to the low incidence of the disease, the level of evidence for different treatment modalities is poor. This review therefore puts different recommendations of clinical management in context and highlights the need for future trials.
Therapeutic advances in medical oncology. 05/2013; 5(3):183-92.
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ABSTRACT: BACKGROUND: Carbonic anhydrase IX (CAIX) is involved in pH homeostasis, growth and survival of tumor cells. Besides the membranous form of CAIX, a soluble form is detectable in serum (s-CAIX). Overexpression of CAIX in tumors offers the opportunity for therapeutic strategies such as CAIX targeting antibodies. The aim of this study was to examine the relationships of CAIX mRNA expression and s-CAIX levels with clinicopathological parameters and survival of patients with primary breast cancer. METHODS: Tumor tissue of 169 primary breast cancer patients was analyzed for RNA expression by microarray analysis (Affymetrix HG-U133A). Concentration of s-CAIX was determined by ELISA in blood samples of 140 patients. RESULTS: In tumor tissue, CAIX mRNA signal intensities (MAS5 values) ranged from 34 to 2,513. Higher CAIX expression was associated with younger age (</≥50 years p = 0.040), negative hormone receptors (estrogen receptor p = 0.004; progesterone receptor p = 0.022) and positive nodal status (p = 0.001) as well as with shorter disease-free survival (p = 0.031). Concentrations of s-CAIX ranged from 56 to 1,500 pg/ml. There was no correlation between s-CAIX and CAIX mRNA levels as well as clinicopathological characteristics or outcome. CONCLUSION: In contrast to reported immunohistochemical studies, we performed RNA-based tissue analyses of CAIX expression and, for the first time, analyzed CAIX serum levels in primary breast cancer. The correlations between CAIX RNA expression and prognostic factors and patient outcome support a biologic role of CAIX in early breast cancer. A role of s-CAIX in primary breast cancer is not supported by our findings.
Journal of Cancer Research and Clinical Oncology 01/2013; · 2.56 Impact Factor
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Histopathology 01/2013; · 3.08 Impact Factor
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ABSTRACT: BACKGROUND: To reduce morbidity of radical groin dissection, the sentinel-node (SLN) procedure was implemented for the treatment of vulvar cancer. It has been proven to be a safe alternative in early-stage disease. Feasibility and safety of the procedure after previous vulvar surgery remain unclear. METHODS: A total of 106 patients with primary vulvar cancer undergoing the SLN procedure were analyzed. Seventy-four patients received the SLN procedure concomitant to vulvar surgery [primary-sentinel group (PSG)], whereas 32 patients had vulvar surgery before secondary SLN [secondary-sentinel group (SSG)]. RESULTS: SLN detection was possible in all patients. Three (9.4 %) patients in the SSG and 30 (40.5 %) in the PSG had metastatic spread to the SLN and underwent radical groin dissection. Median interval between vulva surgery and secondary sentinel was 34 days (range, 7-98). In the SSG tumor, stages were earlier with smaller tumor size (median 19 mm in the PSG vs. 9 mm in the SSG) and lesser invasion depth (4 vs. 2 mm; p < 0.001). There were no groin recurrences in the SSG and 5.4 % in the PSG. No significant difference regarding disease-free survival (DFS) could be detected (3-year DFS of 72.5 % in the PSG compared with 92.5 % in the SSG (median DFS not reached, p = 0.114)). Adjusting for potential confounders (tumor stage, nodal status, tumor size, invasion depth) did not alter the results with regards to DFS. CONCLUSIONS: Our results suggest that a secondary SLN procedure after previous vulvar surgery is feasible and can accurately reflect the groin status of selected patients. Ideally, prospective trials should be conducted to verify accuracy and oncologic safety of the procedure.
Annals of Surgical Oncology 11/2012; · 4.17 Impact Factor
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The Lancet 08/2012; 380(9841):620. · 38.28 Impact Factor
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ABSTRACT: PURPOSE: Conization for suspected high grade cervical intraepithelial neoplasia (CIN) is often performed based on abnormal cytology only. Loop electrosurgical excision procedure (LEEP) is a very common technique in this context. The present study analyses the accuracy of preoperative assessment of CIN with cytology plus colposcopic biopsy and assesses the efficacy of LEEP for the treatment of CIN. METHODS: Two-hundred and sixty-six consecutive patients treated with LEEP for suspected CIN at our center were retrospectively analyzed. Cytology, HPV-DNA testing, colposcopically directed cervical biopsy and/or endocervical curettage were performed to assess cervical lesions before and 3-6 months after surgery. RESULTS: Median age of the patients was 34 years. Median follow-up was 50 months. Preoperative HPV testing was positive for high risk types in 77.9 %. All patients underwent LEEP without further ablative procedures. Complete excision of the lesion could be achieved in 84.3 %; in 13.5 % margins were not securely cleared and in 2.2 % the lesion was not excised entirely. Overall complication rate was 5.4 % (mainly postoperative bleeding and pain). Overall concordance of colposcopic biopsy and cone histology was 85.8 %. The concordance rate was higher for CIN 2/3 (95.1 %) compared with CIN 1 (63.2 %). Nine patients (3.4 %) had persistent disease after 3 months, 4 (1.5 %) developed disease recurrence and underwent re-conization. HPV testing at 3-6 months after surgery was negative in 78.5 %; 2 of the patients developing disease recurrence had a persistent HPV infection after surgery. CONCLUSIONS: Assessment of cervical lesions with colposcopic biopsy is an accurate method (concordance with cone histology 85.8 %). Surgical treatment of high grade CIN with LEEP is a safe procedure with low recurrence rates, resulting in a clearance of cervical HPV infection in the majority of cases.
Archives of Gynecology 08/2012; · 0.91 Impact Factor
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Tobias J Grob,
Uwe Heilenkötter,
Stefan Geist,
Peter Paluchowski,
Christian Wilke,
Fritz Jaenicke,
Alexander Quaas,
Waldemar Wilczak, Matthias Choschzick,
Guido Sauter,
Annette Lebeau
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ABSTRACT: Women with triple-negative breast cancer (TNBC) do not benefit from endocrine therapy or trastuzumab. Chemotherapy is the only systemic therapy currently available. To reduce the elevated risk of disease progression in these patients, better treatment options are needed, which are less toxic and more targeted to this patient population. We performed a comprehensive analysis of potential targetable genetic aberrations affecting the receptor tyrosine kinase/RAS/MAPK pathway, which are observed at higher frequencies in adenocarcinomas of other organs. Sixty-five individual TNBCs were studied by sequence analysis for HER2 (exon 18-23), EGFR (exon 18-21), KRAS (exon 2), and BRAF (exon 15) mutations. In addition, a tissue microarray was constructed to screen for EGFR gene copy gain and EML4-ALK fusion by FISH. Triple-negative status was confirmed by immunohistochemistry and FISH on tissue microarray sections. EGFR and CK5/6 immunohistochemical analyses were performed for identification of the basal-like phenotype. In addition, mutation analysis of TP53 (exon 5-8) was included. Sequence analysis revealed HER2 gene mutation in only one patient (heterozygous missense mutation in exon 19: p.L755S). No mutations were found in EGFR, KRAS, and BRAF. High polysomy of EGFR was detected in 5 of the 62 informative cases by FISH. True EGFR gene amplification accompanied by strong membranous EGFR protein expression was observed in only one case. No rearrangement of the ALK gene was detected. Basal-like phenotype was identified in 38 of the 65 TNBCs (58.5 %). TP53 gene mutation was found in 36/63 (57.1 %) tumors. We conclude that targetable genetic aberrations in the receptor tyrosine kinase/RAS/MAPK pathway occur rarely in TNBC.
Breast Cancer Research and Treatment 05/2012; 134(2):561-7. · 4.43 Impact Factor
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Maike Ihnen,
Kerstin Kress,
Jan Felix Kersten,
Ergin Kilic, Matthias Choschzick,
Hilke Zander,
Volkmar Müller,
Sven Mahner,
Fritz Jänicke,
Linn Woelber,
Karin Milde-Langosch
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ABSTRACT: An altered expression of the activated leukocyte cell adhesion molecule (ALCAM) is associated with cancer progression in various cancer types. In some cancers ALCAM has a prognostic value or is predictive for the benefit of therapeutic interventions. To date there are no data on the role of ALCAM in cervical cancer available.
In this study, ALCAM expression was analysed by immunohistochemistry (IHC) in tissue samples of 233 patients with cervical cancer, among them 178 with complete follow-up information. In addition, soluble (s-)ALCAM was measured in sera of a subset of the included patients (n = 55) by enzyme-linked immunosorbent assay (ELISA).
ALCAM overexpression was detected (immunoreactive score (IRS) 2-12) in 58.4% of the cervical cancer samples. The normal ectocervical or endocervical epithelium showed no ALCAM reactivity. In untreated patients, ALCAM overexpression in tumor tissue tended to be associated with shorter cancer-specific survival (CSS) and disease-free survival (DFS). Patients, whose tumor samples showed ALCAM overexpression receiving a cytotoxic therapy like radiotherapy or chemoradiation, however, had a favourable prognosis compared to those patients, whose cancers showed no or minimal ALCAM staining. This effect was particularly apparent in patients receiving chemoradiation where the CSS was significantly longer in patients with ALCAM-positive tumors (p = 0.038; cumulative incidence rates at 96 months 8%, 95% CI 0%-23%, and 26%, CI 3%-43% in ALCAM-positive and ALCAM-negative cases, respectively).Median preoperative s-ALCAM concentration in sera from tumor patients was 27.6 ng/ml (range 17.5-55.1 ng/ml, mean 28.9 ng/ml), serum levels did not correlate with intratumoral ALCAM expression.
The data of our retrospective study suggest that the prognostic value of ALCAM expression in cervical carcinoma might be therapy-dependent, and that ALCAM might function as a predictive marker for the response to chemoradiation. This should be confirmed in further, prospective studies.
BMC Cancer 04/2012; 12:140. · 3.01 Impact Factor
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ABSTRACT: Cyclin D1 (CCND1) belongs to the family of D-type cyclins involved in cell cycle progression, transcriptional regulation, and cell migration. CCND1 was found to be amplified and overexpressed in a variety of cancers, including some vulvar carcinoma cell lines. To determine the relationship of CCND1 copy number changes and CCND1 protein expression with clinicopathologic features and prognosis, 183 vulvar carcinomas were analyzed on a tissue microarray. Amplification was observed in 32 (22.4%) vulvar cancer specimens and was statistically related to the presence of regional lymph node metastases (P < .001). Detectable CCND1 expression was found in 139 (83.2%) of vulvar carcinomas, and 76 (45.5%) exhibited a moderate or strong expression. Increased levels of CCND1 expression were significantly related to higher patient age (P = .013), positive pN category (P = .004), and negative human papillomavirus status (P < .001). Basaloid as well as verrucous, warty-type, and mixed vulvar carcinomas showed lower CCND1 expression levels than keratinizing or nonkeratinizing tumors (P < .001 and P = .032, respectively). Elevated CCND1 expression levels and amplification of the CCND1 gene were closely connected in the present analysis (P < .001). Patient prognosis was independent from CCND1 amplification status and expression level (P = .57 each). In conclusion, CCND1 is amplified and overexpressed in a substantial proportion of vulvar carcinomas and associated with the occurrence of locoregional lymph node metastases, especially in human papillomavirus-negative tumors.
Human pathology 03/2012; 43(9):1386-93. · 3.03 Impact Factor
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ABSTRACT: Lymph node metastases are the most important prognostic factor for recurrence and survival in vulvar cancer. However, information regarding the impact of the number of positive nodes in vulvar cancer is inconsistent, and so are recommendations when to apply adjuvant radiotherapy.
One hundred fifty-seven consecutive patients with primary squamous cell cancer of the vulva treated at our center were analyzed. All patients underwent primary surgery by triple incision resulting in complete tumor resection.
Median age was 61 years; 49 patients (31%) had lymph node metastases; 21 patients had 1, 13 had 2, and 15 had more than 2 positive lymph nodes. Thirty-two percent of the patients received adjuvant radiotherapy. The risk of lymph node metastases increased with age, greater tumor size, deeper invasion, and higher tumor grade. Median follow-up was 36 months; 23 patients (14.6%) developed disease recurrence (61% vulva, 35% groins, and 4% both). Compared with node-negative patients, survival in all node-positive patients was significantly impaired (P < 0.001; disease-free patients after 2 years: 88% in node-negative patients; 60%, 43%, and 29% in patients with 1, 2, and >2 affected nodes, respectively), whereas no significant difference between the node-positive subgroups could be demonstrated regarding disease-free survival. In multivariate analysis, lymph node status remained the most important prognostic factor regarding disease-free survival, but the effect of positive nodes differed significantly dependent on adjuvant treatment (P = 0.001). In patients without adjuvant radiotherapy to the groins/pelvis, the number of metastatic nodes was highly relevant for prognosis (hazard ratio, 1.752; P < 0.001), whereas this effect disappeared in patients who were treated with adjuvant radiotherapy (hazard ratio, 0.972; P = 0.828).
The negative impact of lymph node metastases is already evident in patients with only 1 affected lymph node. In patients receiving adjuvant radiotherapy, the negative effect of additional lymph node metastases is reduced; adjuvant treatment might therefore be beneficial in patients with only 1 positive node.
International Journal of Gynecological Cancer 03/2012; 22(3):503-8. · 1.65 Impact Factor
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Journal of Clinical Oncology 09/2011; 29(30):e763-5. · 18.37 Impact Factor
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ABSTRACT: Human papillomavirus (HPV)-independent development of vulvar carcinomas is common and the disruption of the TP53 pathway seems to play a key role in these tumors. Overexpression of TP53 in precursor lesions (differentiated VIN) and associated invasive carcinomas is regarded as an important diagnostic feature of this subtype of vulvar cancer. To determine the relationship of TP53 mutation status with clinicopathologic parameters, HPV status, and patient outcome, 18 squamous cell carcinomas of the vulva with TP53 overexpression along with 21 immunohistochemically TP53-negative tumors were analyzed. TP53 mutations were found in 17 (43.6%) of vulvar cancers, 18 (46.2%) tumors were HPV associated, and 8 (20.5%) carcinomas showed no relation to HPV infection or TP53 mutations. The presence of TP53 mutations was significantly linked to TP53 overexpression (P=0.002) and negative HPV status (P=0.012). The specificity of TP53 protein overexpression for the occurrence of TP53 mutations was 68.2%, with a positive predictive value of 66.7%. The most frequent mutation types were C:G →T:A transitions (57.9%). This mutation pattern strongly indicates the important role of oxidative stress in vulvar carcinogenesis. There were no relationships between TP53 mutation status and tumor stage, grading, nodal status, depth of invasion, or patient prognosis. In summary, TP53 mutations play a crucial role in a substantial proportion of vulvar carcinomas and are probably associated to cellular oxidative stress in chronically degenerative diseases of the vulva, such as lichen sclerosus. These data support the potential utility of restoring TP53 function as a therapeutic alternative in vulvar cancer. Further studies are necessary to clarify the prognostic implications of TP53 mutations in vulvar carcinomas.
International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 09/2011; 30(5):497-504. · 2.07 Impact Factor
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ABSTRACT: Vulvar cancer is a rare disease with increasing incidence over the last decades. Treatment includes surgical, radio- and chemotherapeutical options; however, due to the low incidence of the disease and the lack of randomised trials many questions regarding indication of different treatment approaches remain unanswered. This article discusses the current literature to elaborate recommendations for the management of primary vulvar cancer in clinical routine.
We reviewed the available literature on treatment of invasive vulvar cancer with emphasis on therapeutic strategies such as surgery and radio/chemotherapy.
Surgery of the primary tumour and the groins remain the cornerstone of treatment in vulvar cancer with a strong trend towards a less radical approach in early stage disease. Complete vulvectomy was replaced by radical local excision with plastic reconstruction and the sentinel node technique was implemented to avoid the morbidity of complete groin dissection in node negative patients. In patients with advanced primary disease, treatment decisions are still a challenge. Criteria for the indication and performance of chemo/radiotherapy of the vulva/groins/pelvis are still not fully established and vary between different countries and institutions due to the low level of evidence. Often an individualised therapeutic approach aside from guidelines is necessary to treat these patients adequately.
To enable reasonable treatment decisions and avoid unnecessary morbidity, treatment in specialised centres should be intended at any time. Clinical studies performed by several study groups on an international level are urgently needed to further improve therapy.
European journal of cancer (Oxford, England: 1990) 07/2011; 47(15):2315-21. · 4.12 Impact Factor
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ABSTRACT: Carbonic anhydrase IX (CAIX) is a strictly membranous expressed metalloenzyme involved in cell adhesion, pH homeostasis, and cancer progression. This study was designed to assess the role of CAIX in primary ovarian cancer. Two hundred five well-characterized primary ovarian carcinomas were analyzed on a tissue microarray. CAIX expression was determined by immunohistochemistry using a four-step scoring system. Moderate and strong membranous CAIX expression was found in 37 out of 205 (18%) of all assessable ovarian cancer specimens. High levels of CAIX expression were related to mucinous and endometrioid phenotype of ovarian carcinomas (p < 0.05). There was no association between CAIX overexpression and tumor stage, grading, and mitotic count of ovarian carcinomas (p > 0.05). In univariate Cox regression analysis, advanced tumor stage (p < 0.01), high tumor grade (p = 0.017), high mitotic count (p = 0.025), and high CAIX expression levels (p = 0.031) were correlated to shorter overall patient survival. High pT stage (p = 0.036) and CAIX overexpression were connected to poor clinical outcome in endometrioid ovarian carcinomas. Multivariate Cox regression hazard analysis comprising tumor stage, tumor grade, mitotic count, and CAIX expression revealed pT2/3 stage and CAIX overexpression (scores 2 and 3) as independent prognostic markers in ovarian cancer (p < 0.01, each) as well as in the subgroup of endometrioid carcinomas (p < 0.05, each). In conclusion, CAIX is overexpressed in a substantial proportion of mucinous and endometrioid ovarian carcinomas and connected to poor patient outcome. Our data support the potential therapeutic benefit of newly developed targeting antibodies in advanced ovarian cancer.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 06/2011; 459(2):193-200. · 2.49 Impact Factor
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British Journal of Haematology 06/2011; 153(5):544. · 4.94 Impact Factor
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Linn Woelber, Matthias Choschzick,
Christine Eulenburg,
Matthaeus Hager,
Fritz Jaenicke,
Friederike Gieseking,
Lilli Kock,
Maike Ihnen,
Cordula Petersen,
Joerg Schwarz,
Sven Mahner
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ABSTRACT: A tumor-free resection margin of at least 8 mm is considered state of the art in vulvar cancer. This standard is based on small and heterogeneous patient cohorts, and its implementation can result in mutilation.
One hundred two consecutive patients with primary squamous cell vulvar cancer were analyzed. All patients received resection of the primary tumor and the inguinofemoral lymph nodes via three separate incisions, resulting in complete tumor resection. Median follow-up was 31 months. Minimal margin distances were pathologically determined in all dimensions after fixation.
Median age of the patients was 62 years; 38.2% had International Federation of Gynecology and Obstetrics (FIGO) stage I, 17.6% stage II, 24.4% stage III, and 8.8% stage IV disease. The median minimal resection margin was 5 mm (range 0.5-25 mm). Sixteen patients (15.6%) developed disease recurrence, of whom 10 (62.5%) at the vulva. Margin distance had no significant impact on disease-free survival when analyzed continuously (p = 0.388). When cases were divided into three subgroups of <3 mm (28.4%), ≥3 to <8 mm (42.2%), and ≥8 mm (29.4%) resection margin, neither univariate nor multivariate analysis revealed a difference in disease-free survival. There was no significant difference between any of the subgroups regarding tumor stages and adjuvant radiotherapy of the vulva. These results were independent of the direction of the minimal margin distance and consistent when only vulvar recurrences were analyzed.
A tumor-free resection margin is essential for locoregional control in vulvar cancer. However, in this large, single-center study, we could not demonstrate any prognostic impact of pathological margin distance.
Annals of Surgical Oncology 05/2011; 18(13):3811-8. · 4.17 Impact Factor
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ABSTRACT: Despite radical surgery and chemotherapy, most patients with ovarian cancer develop recurrence and die due to progressive disease. To stratify patients for optimal therapy, prognostic and predictive factors are needed. We examined the role of pre- and postoperative CA-125 in this context.
A total of 231 patients with primary ovarian cancer who presented for surgery at our institution between 1996 and 2004 were included in this study (25% FIGO stage I/II and 75% FIGO stage III/IV). The prognostic and predictive values of CA-125 serum concentrations before and after surgery as well as their correlation with clinicopathological variables were analyzed.
Median preoperative CA-125 was 61.6 kU/l (9-1,867 kU/l) in stage I/II patients and 533.15 kU/l (10-22,617 kU/l) in stage III/IV patients. Before surgery, 67% of stage I/II patients and 96% of stage III/IV patients had elevated CA-125 (>35 kU/l). There was a significant decrease in CA-125 after surgery in both patient cohorts (61.6-43.4 kU/l, P = 0.001 and 533.15-92.3 kU/l, P < 0.001, respectively). Furthermore, in stage III/IV patients with complete or so-called optimal (<1 cm residual disease) debulking, preoperative CA-125 levels were significantly lower than in patients with residual disease >1 cm (P = 0.01, P = 0.009, respectively). Neither CA-125 concentration before surgery nor its decrease was prognostically relevant for recurrence and survival at any stage. However, in stage III/IV patients, a high postoperative CA-125 was associated with shorter progression-free survival (P = 0.024).
Although CA-125 serum levels differ significantly before and after surgery in early and advanced-stage ovarian cancer and preoperative CA-125 values correlate with surgical outcome in advanced-stage disease, we could not determine a preoperative cutoff value for prediction of the surgical result. A prognostic relevance was only observed for postoperative CA-125 in stage III/IV patients.
Journal of Cancer Research and Clinical Oncology 02/2011; 137(7):1131-7. · 2.56 Impact Factor
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Linn Woelber,
Kerstin Kress,
Jan F Kersten, Matthias Choschzick,
Ergin Kilic,
Uwe Herwig,
Christoph Lindner,
Joerg Schwarz,
Fritz Jaenicke,
Sven Mahner,
Karin Milde-Langosch,
Volkmar Mueller,
Maike Ihnen
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ABSTRACT: Carbonic anhydrase IX (CAIX) is a membranous expressed metalloenzyme involved in pH homeostasis and cell adhesion. The protein is overexpressed in a variety of tumors and potentially associated with negative outcome. This study was designed to investigate the prognostic role of CAIX in serum and tumor tissue of patients with primary cervical cancer.
Tumor samples of 221 consecutive patients with primary cervical cancer who underwent surgery between 1993 and 2008 were analyzed for CAIX expression by immunohistochemistry. Additionally, preoperative serum CAIX concentrations were determined by ELISA in a subset of patients. Correlation with intratumoral CAIX expression as well as clinicopathological factors and outcome was analyzed.
CAIX expression was observed in 81.9% of the tumor specimens; 62.0% showed a moderate or strong staining intensity. Moderate/strong expression was associated with squamous histology (p=0.024), advanced tumor stage (p=0.001), greater invasion depth (p=0.025), undifferentiated tumor grade (p<0.001) and high preoperative SCC-Ag values (p=0.042). Furthermore patients with moderate/strong intratumoral CAIX expression had a higher number of metastatic lymph nodes compared to those with none/weak intratumoral expression levels (p=0.047) and there was a non-significant association between high intratumoral CAIX expression and shorter survival (p=0.118). Preoperative serum concentrations of CAIX ranged between 23 and 499 pg/mL and did not correlate with intratumoral expression or other clinicopathological variables.
CAIX is associated with advanced tumor stages and lymph node metastases in cervical cancer, potentially representing a new target in this disease. In contrast to other epithelial cancers we could not observe a correlation between serum CAIX and its intratumoral expression.
BMC Cancer 01/2011; 11:12. · 3.01 Impact Factor
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ABSTRACT: Therapeutic options in advanced or recurrent vulvar cancer are limited. The identification of new prognostic factors and markers for therapy stratification is therefore highly desirable. Carbonic anhydrase IX (CAIX) is up-regulated in various solid tumors and a promising new target. We therefore determined CAIX serum concentration and its prognostic relevance in correlation to intratumoral CAIX expression in patients with primary vulvar cancer.
Thirty-one serum samples of patients with primary vulvar cancer were prospectively collected before surgery and analyzed for CAIX by enzyme-linked immunosorbent assay. In addition, intratumoral CAIX expression was determined by immunohistochemistry and correlation with serum CAIX and clinicopathological factors, and outcome was analyzed.
Preoperative serum concentration of CAIX ranged between 56 and 879 pg/mL (median, 147 pg/mL; mean, 237.29) and was significantly higher in patients with high intratumoral expression (median, 269 pg/mL vs 126 pg/mL, P = 0.03). High serum CAIX was not associated with any of the analyzed clinicopathological parameters. However, disease-free survival was shorter in patients with high preoperative serum CAIX (above median; P = 0.012). By immunohistochemistry, 26% of the tumors showed a moderate or strong expression of CAIX, whereas 74% showed weak or no expression. High intratumoral expression of CAIX was also associated with unfavorable disease-free survival (P = 0.043).
Carbonic anhydrase IX serum concentration is higher in patients with high intratumoral expression, and elevated preoperative serum values are associated with unfavorable prognosis. Serum CAIX might therefore be an easily assessable marker to stratify patients for adjuvant therapy and potentially monitor response. Carbonic anhydrase IX is differentially expressed in vulvar cancer and potentially associated with negative outcome.
International Journal of Gynecological Cancer 01/2011; 21(1):141-8. · 1.65 Impact Factor
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Andreas H Marx,
Eike C Burandt, Matthias Choschzick,
Ronald Simon,
Emre Yekebas,
Jussuf T Kaifi,
Martina Mirlacher,
Djordje Atanackovic,
Carsten Bokemeyer,
Walter Fiedler,
Luigi Terracciano,
Guido Sauter,
Jakob R Izbicki
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ABSTRACT: HER-2 is the molecular target for antibody-based treatment of breast cancer (trastuzumab). The potential benefit of anti-HER-2 therapy is currently investigated in several other HER-2 amplified cancers. For example, trastuzumab was recently shown to be effective in HER-2 positive gastric cancer. To address the potential applicability of anti-HER-2 therapy in colorectal cancer, tissue microarray sections and colorectal resection specimens of 1851 colorectal cancers were analyzed for HER-2 overexpression and amplification using FDA approved reagents for immunohistochemistry and fluorescence in situ hybridization. HER-2 amplification was seen in 2.5% and HER-2 overexpression in 2.7% of 1439 interpretable colorectal cancers. Amplification was often high level with HER-2 copies ranging from 4 to 60 per tumor cell and was strongly related to protein overexpression. HER-2 amplification and overexpression were unrelated to histological tumor type, tumor localization, grading, pT, pN, pM or survival. As heterogeneity of drug target expression could represent a major drawback for targeted cancer therapy we next studied HER-2 heterogeneity in selected cases. Extensive evaluation of all available large sections from patients with HER-2 positive colorectal cancer revealed heterogenous findings in 3 of 4 cases. In summary, high-level HER-2 amplification occurs in a small fraction of colorectal cancers. Heterogeneity of amplification may limit the utility of anti- HER-2 therapy in some of these tumors and therefore, adequate clinical trials are needed to further evaluate this approach.
Human pathology 11/2010; 41(11):1577-85. · 3.03 Impact Factor
