Unrealistic expectations for IR microspectroscopic imaging.
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Diagnosis, Differential↗
Biomedical subjects
Lars-Christian Horn
Publications and source records attributed to Lars-Christian Horn.
Expression of erythropoietin and erythropoietin receptor in cervical cancer and relationship to survival, hypoxia, and apoptosis.
PURPOSE: Physiologically, hypoxia induces the expression of erythropoietin (Epo) in adult kidney cells. Epo, in turn, acts on the Epo receptor (EpoR) in RBC precursors to stimulate growth and prevent apoptosis. Because hypoxia plays a major role in the malignant progression of tumors and Epo and its receptors have also been detected in malignant tumors, we investigated the expression of Epo and EpoR and their relationship with hypoxia, proliferation, apoptosis, and clinicopathologic variables in cervical cancer. EXPERIMENTAL DESIGN: Intratumoral oxygen measurement and needle biopsies of the tumors were done in 48 patients with cervical cancer. The obtained tissue was analyzed by immunohistochemistry with antibodies against Epo, EpoR, and Ki-67 as well as by terminal deoxynucleotidyl transferase-mediated deoxyuracil triphosphate nick-end labeling assays. RESULTS: Epo and EpoR were expressed in 88% and 92% of samples, respectively. Cervical cancers with higher Epo expression showed a significantly reduced overall survival (3 years, 50.0% versus 80.6%; P = 0.0084). Epo and EpoR expression correlated significantly with apoptosis (r = 0.49, P = 0.001 and r = 0.36, P = 0.021). Furthermore, EpoR expression correlated significantly with tumor size (r = 0.32, P = 0.032) and was significantly associated with the presence of lymphovascular space involvement (P = 0.037). However, we observed no correlation between Epo or EpoR expression and intratumoral hypoxia, although in well-oxygenated tumors, EpoR localized significantly more often to the invasion front (P = 0.047). CONCLUSIONS: This study analyzes Epo/EpoR expression and their relationship with intratumoral pO(2) levels as well as with survival in patients with cervical cancer. The data suggest a critical role of the endogenous Epo/EpoR system in cervical cancer.
Adult↗
Anatomical landmarks of radical prostatecomy.
INTRODUCTION: In the present study, we review current literature and based on our experience, we present the anatomical landmarks of open and laparoscopic/endoscopic radical prostatectomy. METHODS: A thorough literature search was performed with the Medline database on the anatomy and the nomenclature of the structures surrounding the prostate gland. The correct handling of puboprostatic ligaments, external urethral sphincter, prostatic fascias and neurovascular bundle is necessary for avoiding malfunction of the urogenital system after radical prostatectomy. RESULTS: When evaluating new prostatectomy techniques, we should always take into account both clinical and final oncological outcomes. The present review adds further knowledge to the existing "postprostatectomy anatomical hazard" debate. It emphasizes upon the role of the puboprostatic ligaments and the course of the external urethral sphincter for urinary continence. When performing an intrafascial nerve sparing prostatectomy most urologists tend to approach as close to the prostatic capsula as possible, even though there is no concurrence regarding the nomenclature of the surrounding fascias and the course of the actual neurovascular bundles. After completion of an intrafascial technique the specimen does not contain any periprostatic tissue and thus the detection of pT3a disease is not feasible. This especially becomes problematic if the tumour reaches the resection margin. DISCUSSION: Nerve sparing open and laparoscopic radical prostatectomy should aim in maintaining sexual function, recuperating early continence after surgery, without hindering the final oncological outcome to the procedure. Despite the different approaches for radical prostatectomy the key for better results is the understanding of the anatomy of the bladder neck and the urethra.
Endoscopy↗
Tumor hypoxia and expression of c-met in cervical cancer.
OBJECTIVES: Hypoxia enhances malignant progression by promoting the development of metastases and increasing invasiveness. One key regulator that controls growth, invasion and metastasis in cancer cells is the growth factor receptor c-met. The aim of this study, therefore, was to investigate the expression of the c-met protooncogene in cervical cancers in relation to intratumoral hypoxia levels and to clinico-pathological parameters. METHODS: 43 Patients with cervical cancer were subjected to intratumoral pO(2) measurement with the Eppendorf electrode and biopsies were taken. The tissue was subsequently analyzed by immunohistochemistry with an anti-c-met antibody. RESULTS: c-met was expressed in 72% of cervical cancers. There was a significantly stronger expression in poorly differentiated tumors (r=0.4, p=0.008). Furthermore, c-met expression was significantly associated with a spray-like pattern of invasion (p=0.008). However, there was no significant relationship between c-met expression and intratumoral hypoxia, pT stage, FIGO stage, lymphovascular space involvement, tumor size or overall survival. CONCLUSIONS: Although c-met has been shown to be hypoxia-induced in vitro, our results suggest that it is not the mediator of deleterious effects of hypoxia on clinical outcome in cervical cancer.
Adult↗
Umbilical cord hypercoiling and thinning: a rare cause of intrauterine death in the second trimester of pregnancy.
Little attention has been paid to the pathologic features of the umbilical cord, which might fatally damage the fetus. We determined the association of hypercoiling (more than 1 coil per 5 cm) and thinning with consecutive constriction of the umbilical vessels (thin cord syndrome; TCS) and intrauterine fetal death (IUFD). Three hundred and three cases of consecutive fetal autopsies over a 5-year period, including spontaneous and induced abortions of the 2nd trimester of pregnancy, were examined using a standardized protocol. The mean maternal age was 28.5 years and the mean gestational age was 19.1 weeks (range: 12.6 to 24.5 weeks). Thirty-six percent of all cases were induced abortions because of congenital malformations, and 8.9% resulted from legal abortions, as regulated by German law. One hundred sixty-seven cases (55.1%) were spontaneous abortion specimens. The leading cause for IUFD in the spontaneous abortion group was an amnion infection (34.7%), followed by abruptio placentae (15.6%). In 25.1% of cases, placental dysmaturity with consecutive placental insufficiency was responsible for IUFD. Pathologies of the umbilical cord as the cause of IUFD were seen in 10.2% of the cases. Most of these cases (15/17) involved TCS. In 14.4% of all spontaneous abortion specimens the cause of IUFD could not be determined by autopsy. There was an apparent difference in the frequency of TCS in the spontaneous abortion group (15/167 = 9%) compared to the nonspontaneous group (2/136 = 1.5%). A remarkably high percentage (17/303 = 5.6%) of all cases showed TCS. In cases of spontaneous abortions, TCS was causative for intrauterine death in 9% of cases (15/167). Careful pathologic examination of the umbilical cord is recommended to detect TCS and to reduce the cases with unexplained intrauterine death.
Aborted Fetus↗
Diversity of CD97 in smooth muscle cells.
CD97, an epidermal growth factor (EGF)-TM7 receptor, is not restricted to hematopoetic and carcinoma cells but is also found on smooth muscle cells (SMC). We have examined its location and biochemical structure in various normal and tumorigenic SMC-containing tissues. SMC of the urinary bladder, lung bronchi and bronchioles, myometrium, and gastrointestinal tract were immunohistologically stained by using monoclonal antibodies (mabs) to the CD97 stalk region (CD97(stalk)). Mabs directed against an N-glycosylation-dependent epitope within the EGF-domains (CD97(EGF)) did not bind to normal SMC. Vascular SMC, which was also CD97(EGF)-negative, showed further CD97 heterogeneity. Only a few, if any, SMC from the aorta or elastic arteries of the systemic circulation were positive for CD97 mRNA and therefore also for CD97(stalk). CD97(stalk)-positive SMC were slightly more numerous in muscular and peripheral arteries. In contrast, most venous SMC expressed CD97(stalk). A comparison with other SMC molecules revealed a similar but not identical staining pattern for CD97(stalk) and desmin. Further CD97 heterogeneity was observed during SMC transformation. All leiomyomas (n=5) and nine out of 21 leiomyosarcomas were positive for both CD97(stalk) and CD97(EGF). As expected, CD97(EGF)-positive SMC tumors expressed partly N-glycosylated CD97. Seven out of 21 leiomyosarcomas were completely devoid of CD97. Thus, CD97 showed variable expression in vascular and biochemical modification in tumorigenic SMC, suggesting that the function of the molecule is specific for the SMC subtype.
Adult↗
Mixed small cell carcinomas of the uterine cervix: prognostic impact of focal neuroendocrine differentiation but not of Ki-67 labeling index.
Small cell neuroendocrine carcinomas sometimes represent a non-small cell component. Because of infection with the high-risk human papillomavirus of small cell carcinomas (SmCCs), several host cell regulatory proteins are altered, thus causing altered proliferative activity. Knowledge regarding the prognostic impact of focal neuroendocrine differentiation in mixed SmCCs and the value of proliferative activity in these tumors is very limited. Small cell carcinomas were selected for immunohistochemical staining with neuroendocrine markers and Ki-67. In cases with mixed tumors, the percentage of the SmCC component was calculated and correlated with survival. Of 677 tumors, 9 (1.3%) were classified as SmCCs after Grimelius staining (8/9 positive tumors) and immunohistochemical reaction against neuron-specific enolase, chromogranin A, synaptophysin (7/9 positive tumors), and CD56 (8/9 positive tumors); all specimens were positive for at least 2 of these. CD99 staining was completely negative. Two thirds of the SmCCs showed non-small cell differentiation. Four patients died of the tumor after a median time of 36.7 months (range, 15-56 months). Even an SmCC component of 17% was associated with a fatal course. Small cell carcinoma represented a significantly lower proliferation (Ki-67 labeling index) than did the non-small cell component in the same tumor (12.8% vs 70.8%; P < .001). Even a small SmCC component in mixed carcinomas of the uterine cervix was associated with adverse outcome. Proliferative activity, determined by Ki-67 labeling index, is of no prognostic value.
Adult↗
p16, p14, p53, cyclin D1, and steroid hormone receptor expression and human papillomaviruses analysis in primary squamous cell carcinoma of the endometrium.
Pathogenetically, endometrioid adenocarcinomas of the endometrium are associated with hyperestrogenism and serous papillary carcinomas with alterations of p53. The etiology of primary endometrial squamous cell carcinoma (ESCC), however, is speculative. The purpose of this study was to evaluate the role of p14, p16, p53, cyclin D1, steroid hormone receptors, and human papillomaviruses (HPV) infection in the pathogenesis of primary endometrial squamous cell carcinoma. The expression of p16, p14, p53, cyclin D1, and steroid hormone receptors (estrogen, progesterone, and androgen) was examined immunohistochemically in 8 primary ESCCs. HPV analysis was performed using general primers and HPV typing. The median age of the patients was 62.1 years. Four cases showed positive nuclear and cytoplasmic p16 staining in an insular pattern, and 1 case nuclear positivity for p53 and estrogen receptors, respectively. Four of 8 cases were positive for progesterone receptor analysis and cyclin D1. All cases were negative for p14 and androgen receptor staining. All but one case were negative for HPV analysis. Five patients were alive with and without evidence of disease after a mean follow-up of 6.1 years. The results of this study suggest that alterations of the p16 pathway may play an etiologic role in at least a proportion of the ESCC, but without any association to HPV infection. Factors known to play a pathogenetic role in types 1 and 2 of endometrial carcinomas are not associated with primary ESCC. However, prognostically, ESCCs are more related to type 1 cancers.
Adult↗
The status of cyclooxygenase-2 expression in ductal carcinoma in situ lesions and invasive breast cancer correlates to cyclooxygenase-2 expression in normal breast tissue.
OBJECTIVES: There is a paucity of data on cyclooxygenase (COX)-2 expression in normal breast tissue and on the changes in COX-2 expression from normal tissue via ductal carcinoma in situ (DCIS) lesions to invasive cancer. The aim of this study, therefore, was to investigate COX-2 protein expression in normal breast tissue, DCIS, and invasive breast cancer in samples from the same patients. METHODS: In 39 patients, we investigated and compared COX-2 expression in paired samples of invasive cancer and normal adjacent breast epithelium by immunohistochemistry with a monoclonal COX-2 antibody. Furthermore, in 29 of these cases, we also analyzed a concomitant DCIS lesion. RESULTS: Patients without COX-2 expression in normal breast tissue also do not express COX-2 in invasive breast cancer and in DCIS lesions, respectively. Conversely, COX-2 expression in normal breast tissue was an indicator for COX-2 expression in the paired breast tumors. There was no significant correlation between COX-2 expression and pathologic tumor stage, nodal status, hormone receptor status, tumor size, grading, and lymphovascular space involvement. CONCLUSIONS: This is the largest study to date investigating COX-2 in paired samples of breast tumors and normal adjacent breast tissue. Our data are consistent with the hypothesis that COX-2 overexpression is an early event in breast carcinogenesis.
Adult↗
Combined three-dimensional microscopic visualisation of tumour-invasion front of cervical carcinoma.
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Carcinoma, Squamous Cell↗
p16, p14, p53, and cyclin D1 expression and HPV analysis in small cell carcinomas of the uterine cervix.
Small cell carcinomas (SmCCs) of the uterine cervix are rare tumors. The knowledge regarding protein expression of several checkpoint candidates of cell cycle regulation is limited. Surgically treated SmCCs were selected from our files for immunohistochemical staining (neuroendocrine markers, p53, p16, p14, and cyclin D1). Polymerase chain reaction analysis, using general primers, was performed for human papillomavirus analysis. Nine of 677 tumors (1.3%) were classified as SmCCs after Grimelius staining (8/9 tumors positive) and immunohistochemical reaction against neurone-specific enolase, chromogranin A, synaptophysin (7/9 positive tumors), and CD 56 (8/9 positive tumors). All specimens were positive for at least two of the above. Two SmCCs were p53 positive and one case was p14 positive. Cyclin D1 staining was completely negative. All cases showed strong nuclear and/or cytoplasmic p16-immunostaining. Seven tumors represented human papillomavirus positivity for high-risk types. Four patients died of the tumor after a median time of 36.7 months (range, 15-56 months), representing a 5-year survival rate of 56%. The results suggest that p16 is up-regulated or accumulated in the SmCCs of the uterine cervix, probably caused by infection with human papillomavirus. p14 inactivation is of high prevalence in SmCCs and detection rate of p53 is similar to other histologic types of cervical carcinomas.
Adult↗
Serous carcinoma of the endometrium with choriocarcinomatous differentiation: a case report and review of the literature indicate the existence of 2 prognostically relevant tumor types.
Nongestational choriocarcinomas rarely occur outside the gonads or teratomas. We report a serous carcinoma of the endometrium with a choriocarcinomatous component and review of the literature. A 61-year-old woman underwent hysterectomy and bilateral salpingo-oophorectomy for a serous carcinoma with choriocarcinomatous component. Immunohistochemistry showed a strong p53 staining of the serous component and the cytotrophoblastic cells of the choriocarcinomatous component; the syncytiotrophoblast was negative. The initial serum human chorionic gonadotropin (hCG) was 225,000 IU/L. Postoperatively, the patient developed diffuse pulmonary metastatic disease. Despite chemotherapy, the patient died 2 months after initial diagnosis. Abstracting the data from the reported cases and from the literature, it can be assumed that 2 different tumor types exist. The first one is morphologically and clinically more related to the gestational choriocarcinoma with strongly elevated serum hCG levels, early onset of (distant) metastatic disease, and consecutively rapid and often fatal clinical course. The second type presents as an endometrial carcinoma with single syncytiotrophoblast-like cells, associated with low serum hCG, no distant metastatic disease, and, consequently, a better prognosis. The prognostically relevant component for long-time survival in the latter variant is the nontrophoblastic component.
Adenocarcinoma↗
Clonal history of papillomavirus-induced dysplasia in the female lower genital tract.
BACKGROUND: Dysplastic lesions of the vagina or the vulva often occur in women who have a previous history of cervical dysplasia. Most lesions in the female lower genital tract are induced by infections with high-risk oncogenic human papillomaviruses (HR-HPVs), including HPV16 and HPV18. HR-HPV genomes frequently integrate into host cell chromosomes at random sites. We analyzed viral integration sites in multiple metachronous lesions of the lower genital tract from women previously treated for HR-HPV-positive cervical dysplasia or cancer to determine whether the metachronous lesions emerged from a single common preexisting dysplastic cell clone or as consequence of independent HR-HPV infection events in the female lower genital tract. METHODS: From among 1500 patients with anogenital lesions, seven patients with high-grade vaginal or vulvar lesions and with a previous history of cervical disease (five with prior high-grade cervical dysplasia and two with a history of cervical cancer) were included in this study. Integration sites of HPV16 or HPV18 in vaginal or vulvar lesions were mapped by an adaptor ligation polymerase chain reaction (PCR) method. The sequence information was used to design an integrate-specific PCR assay that was applied to DNA extracted from archival paraffin-embedded material derived from biopsy samples of cervical lesions. RESULTS: Identical HPV DNA integration loci were found in vaginal or vulvar and cervical samples of all lesions available for four of the five patients with a prior history of high-grade cervical dysplasia and for both patients with a history of cervical cancer. CONCLUSIONS: These data indicate that high-grade dysplastic lesions in the female lower genital tract may emerge primarily as monoclonal lesions from a transformed cell population derived from the uterine cervix.
Adult↗
Delimitation of squamous cell cervical carcinoma using infrared microspectroscopic imaging.
Infrared (IR) spectroscopic imaging coupled with microscopy has been used to investigate thin sections of cervix uteri encompassing normal tissue, precancerous structures, and squamous cell carcinoma. Methods for unsupervised distinction of tissue types based on IR spectroscopy were developed. One-hundred and twenty-two images of cervical tissue were recorded by an FTIR spectrometer with a 64x64 focal plane array detector. The 499,712 IR spectra obtained were grouped by an approach which used fuzzy C-means clustering followed by hierarchical cluster analysis. The resulting false color maps were correlated with the morphological characteristics of an adjacent section of hematoxylin and eosin-stained tissue. In the first step, cervical stroma, epithelium, inflammation, blood vessels, and mucus could be distinguished in IR images by analysis of the spectral fingerprint region (950-1480 cm(-1)). In the second step, analysis in the spectral window 1420-1480 cm(-1) enables, for the first time, IR spectroscopic distinction between the basal layer, dysplastic lesions and squamous cell carcinoma within a particular sample. The joint application of IR microspectroscopic imaging and multivariate spectral processing combines diffraction-limited lateral optical resolution on the single cell level with highly specific and sensitive spectral classification on the molecular level. Compared with previous reports our approach constitutes a significant progress in the development of optical molecular spectroscopic techniques toward an additional diagnostic tool for the early histopathological characterization of cervical cancer.
Carcinoma, Squamous Cell↗
Association between the mesenchymal compartment of uterovaginal organogenesis and local tumour spread in stage IB-IIB cervical carcinoma: a prospective study.
BACKGROUND: Macroscopic, microscopic, and occult local tumour spread might be restricted to a permissive territory related to the morphogenesis of the tissue or organ from which the tumour originates. We aimed to define such a morphogenetic unit in Müllerian development, and to assess the role of total mesometrial resection in the treatment of patients with stage IB-IIB cervical carcinoma. METHODS: We analysed uterovaginal development in serial sections of female human embryos and fetuses, and defined the distal Müllerian morphogenetic unit from the Müllerian mesenchyme. We assessed prospectively the histopathological and clinical findings from patients who underwent total mesometrial resection-modified surgery for stage IB-IIB cervical carcinoma that aims to remove the uterus, proximal vagina, and extracervical mesenchyme within the borders of the distal Müllerian morphogenetic unit. FINDINGS: The spatial extension of the Müllerian mesenchyme, its vascularisation, and its innervation during early uterovaginal organogenesis determine a tissue territory that can be followed during fetal development and identified in women as a morphogenetic unit. 105 of 106 patients who had total mesometrial resection, 63 of whom were classed as high risk, had microscopically tumour-free resection margins (ie, R0). 48 (96%) of 50 patients had pelvic recurrence-free survival at 3 years (95% CI 92-100) without adjuvant radiotherapy. INTERPRETATION: Radical en-bloc resection of a topographically defined anatomical territory derived from common precursor tissue leads to local tumour control, preservation of autonomic nerves, and a reduced need for adjuvant radiotherapy.
Adult↗
Hormone replacement therapy (HRT) and endometrial morphology under consideration of the different molecular pathways in endometrial carcinogenesis.
The majority of modern hormone replacement therapy (HRT) regimens contain estrogen and progestogens, given either in a cyclical or continuous manner. About 15% of the endometrial biopsies taken from women on sequential HRT show proliferative activity including atypical endometrial hyperplasia in up to 1% of the cases. The majority of biopsies from women under continuous combined HRT show an endometrial atrophy. About 2-3% of these women will present proliferative activity, usually without atypical hyperplasia. Contrary to breast cancer, an increased risk of endometrial cancer has not been reported in the WHI- and HERS-studies. However, endogenous factors, such as obesity, diabetes mellitus, the distribution of estrogen receptors alpha and beta and genetic polymorphisms for receptors and enzymes might alter the endometrial stimulation under different types of HRT. There should be a liberal indication for endometrial biopsies in Hereditary Non-Polyposis Colorectal Cancer (HNPCC). HNPCC-patients under HRT as well as for ultrasonographic evaluation of the endometrium. The risk of atypical hyperplasias or carcinoma under unopposed estrogen-therapy varies from 2 to 10%. So, this kind of HRT should not be used in non-hysterectomised women. As far as the risk of endometrial cancer under any kind of HRT is concerned, the different molecular pathways of endometrial carcinogenesis (type 1 and 2 cancers) should be taken into account. The use of tibolone leaves the endometrium unaffected.
Endometrial Neoplasms↗
A misdiagnosed case of caesarean scar pregnancy.
CASE REPORT: We report a case of an ectopic pregnancy in a caesarean section scar, which was initially misdiagnosed despite using ultrasound. For the first time, a strongly vascularised pelvic tumour developed while the titre of serum human chorionic gonadotrophin decreased after a curettage abortion for an unwanted pregnancy. OUTCOME: Due to uncontrollable haemorrhage, an emergency hysterectomy had to be performed 8 weeks later.
Adult↗
Expression of Apaf-1 in cervical cancer correlates with lymph node metastasis but not with intratumoral hypoxia.
OBJECTIVES: The aim of this study was to investigate the expression of the proapoptotic protein Apaf-1 in cervical cancers. Moreover, we studied its correlation to intratumoral pO(2) and to clinico-pathological parameters. METHODS: 86 patients with cervical cancer were subjected to intratumoral pO(2) measurement with the Eppendorf electrode. From these patients, cervical cancer tissue was used for immunohistochemistry with an anti-Apaf-1 antibody. RESULTS: Apaf-1 is expressed in cervical cancer. Cervical cancers with strong or moderate Apaf-1 expression had significantly less lymph node metastases at time of surgery than tumors with weak or negative Apaf-1 expression (P = 0.022). There was no significant correlation between Apaf-1 expression and intratumoral pO(2), pT stage, FIGO stage, lymphovascular space involvement, and grade. CONCLUSIONS: Loss of Apaf-1 expression may represent a marker of aggressive tumor behavior since it correlates significantly with the occurrence of lymph node metastasis in cervical cancer.
Adult↗