All means all: An introduction to the 2020 Global Education Monitoring Report on inclusion.

This article provides an overview of the 2020 Global Education Monitoring Report, which looks at social, economic, and cultural mechanisms that discriminate against disadvantaged children, youth, and adults, keeping them out of education or marginalized in it. Countries are expanding their vision of inclusion in education to put diversity at the core of their systems. Yet, implementation of well-meaning policies often falters. Released at the start of the Decade of Action to 2030, and during the Covid-19 crisis, which has exacerbated underlying inequalities, the report argues that resistance to addressing every learner's needs is a real threat to achieving global education targets. Inclusion and Education: All Means All identifies practices in governance and finance; curricula, textbooks, and assessments; teacher education; school infrastructure; and relations with students, parents, and communities that can unlock the process to inclusion. It provides policy recommendations to make learner diversity a strength to be celebrated, a force for social cohesion.

[3 unusual courses of gastrointestinal MALT lymphoma]. / 3 ungewöhnliche Verläufe von gastrointestinalen MALT-Lymphomen.

We report on the unusual course of disease in three patients with gastrointestinal MALT lymphoma. Special features are the primary lymphoma manifestation, the high-grade transformation during the follow up, the long-time interval between initially curative intended therapy and relapse and the occurrence of another neoplasia in one case. This demonstrates that despite their good prognosis in general, follow-up investigations of gastrointestinal MALT lymphoma are reasonable.

Inflammatory response in serrated precursor lesions of the colon classified according to WHO entities, clinical parameters and phenotype-genotype correlation.

Studies on traditional serrated adenoma (TSA) and sessile serrated adenoma with dysplasia (SSA-D) are rare due to the low frequency of these lesions, which are well defined by the latest WHO classification. However, introducing new morphological criteria such as intra-epithelial lymphocytes (IELs) might facilitate colorectal polyp diagnoses. Additionally, the phenotype-genotype correlation needs to be updated as the terminology has repeatedly changed. This study analysed 516 polyps, consisting of 118 classical adenomas (CAD), 116 hyperplastic polyps (HPP), 179 SSAs, 41 SSA-Ds, and 62 TSAs. The lesions were analysed in relation to the patients' clinical parameters including gender, age, localisation, and size. The inflammatory background of the polyps was quantified and BRAF and KRAS mutations as well as MLH1 and CDKN2A promoter methylation were assessed. In multivariate analyses, an increase in IELs was an independent and robust new criterion for the diagnosis of SSA-D (p < 0.001). Superficial erosions and acute neutrophil granulocytes led to reactive changes potentially resembling dysplasia. KRAS and BRAF mutations were associated with CAD/TSA and HPP/SSA, respectively. However, almost half of TSAs had a BRAF mutation and were KRAS wild type. CDKN2A seems to precede MLH1 hyper-methylation within the serrated carcinogenesis model. The genotyping of WHO-based entities - and especially SSA - has sharpened in comparison to previously published data. TSAs can be sub-grouped according to their mutation status. Of note, the higher number of IELs in SSA-D reflects their close relationship to colorectal cancers with micro-satellite instability. Therefore, IELs might represent a new diagnostic tool for SSA-D.

Loss of DOG-1 expression associated with shift from spindled to epithelioid morphology in gastric gastrointestinal stromal tumors with KIT and platelet-derived growth factor receptor α mutations.

Most gastric gastrointestinal stromal tumors (GISTs) display spindle cell morphology and coexpress CD117 (KIT), DOG-1, and CD34. Secondary loss of DOG-1 has not been reported. We present two gastric GISTs which showed loss of DOG-1 in the epithelioid component but retained its expression in the minor spindle cell component. Patients were a 67-year-old man and an 80-year-old woman with 4.8-cm and 3.5-cm gastric GISTs harboring mutations in KIT exon 11 (c.1729_1758dup30; p.P577_R586dup) and platelet-derived growth factor receptor α (PDGFRA) exon 18 (c.2527_2538del12; p.I843_D846del), respectively. Both were predominantly epithelioid with a minor microscopic spindle cell component (3-12 mm). The spindle cell component was CD117(+)CD34(+)DOG-1(+) in both cases. The epithelioid component in case 1 was CD117(+)CD34(+)DOG-1(-). In case 2, the epithelioid component strongly expressed PDGFRA (dot-like) but lost CD117, CD34, and DOG-1. These cases confirm the immunophenotypic heterogeneity as secondary events in GIST. Loss of DOG-1 in KIT-negative PDGFRA mutants should not preclude diagnosis.

Performance of an online translation tool when applied to patient educational material.

BACKGROUND: Language barriers may prevent clinicians from tailoring patient educational material to the needs of individuals with limited English proficiency. Online translation tools could fill this gap, but their accuracy is unknown. We evaluated the accuracy of an online translation tool for patient educational material. METHODS: We selected 45 sentences from a pamphlet available in both English and Spanish, and translated it into Spanish using GoogleTranslate™ (GT). Three bilingual Spanish speakers then performed a blinded evaluation on these 45 sentences, comparing GT-translated sentences to those translated professionally, along four domains: fluency (grammatical correctness), adequacy (information preservation), meaning (connotation maintenance), and severity (perceived dangerousness of an error if present). In addition, evaluators indicated whether they had a preference for either the GT-translated or professionally translated sentences. RESULTS: The GT-translated sentences had significantly lower fluency scores compared to the professional translation (3.4 vs. 4.7, P < 0.001), but similar adequacy (4.2 vs. 4.5, P = 0.19) and meaning (4.5 vs. 4.8, P = 0.29) scores. The GT-translated sentences were more likely to have any error (39% vs. 22%, P = 0.05), but not statistically more likely to have a severe error (4% vs. 2%, P = 0.61). Evaluators preferred the professional translation for complex sentences, but not for simple ones. DISCUSSION: When applied to patient educational material, GT performed comparably to professional human translation in terms of preserving information and meaning, though it was slightly worse in preserving grammar. In situations where professional human translations are unavailable or impractical, online translation may someday fill an important niche.

Colonization of experimental murine breast tumours by Escherichia coli K-12 significantly alters the tumour microenvironment.

The successful application of live bacteria in cancer therapy requires a more detailed understanding of bacterial interaction with the tumour microenvironment. Here, we analysed the effect of Escherichia coli K-12 colonization on the tumour microenvironment by immunohistochemistry and fluorescence microscopy in the murine 4T1 breast carcinoma model. We described the colonization of tumour-bearing mice, as well as the spatiotemporal distribution of E. coli K-12 in the 4T1 tumour tissue over a period of 14 days. The colonization resulted within 3 days in large avascular necrotic tissue, redistribution of hypoxic areas and an enhanced collagen IV deposition within the colonized tumour tissue, which changed the tumoral perfusion of systemically injected immunoglobulins. In addition, E. coli K-12 colonization led to the redistribution of tumour-associated macrophages, forming a granulation tissue around bacterial colonies, and also to an increase in TNFalpha and matrix metalloproteinase 9 expression. Colonization of 4T1 tumours by E. coli K-12 resulted in strong reduction of pulmonary metastatic events. These new insights will contribute to the general understanding of the tumour-microbe cross-talk and to the design of bacterial strains with enhanced anticancer efficiency.

Immunostaining for p16INK4a used as a conjunctive tool improves interobserver agreement of the histologic diagnosis of cervical intraepithelial neoplasia.

The quality of cervical histopathology is critical to cervical cancer prevention, cancer treatment, and research programs. On the basis of the histology results further patient management is determined. However, the diagnostic interpretation of histologic hematoxylin-eosin (H&E)-stained slides is affected by substantial rates of discordance among pathologists. Overexpression of the cyclin-dependent kinase inhibitor p16INK4a, a cell cycle regulating protein, has been shown to be strongly correlated with dysplastic lesions of the cervix uteri. In this study, we assessed whether p16INK4a immunohistochemistry may increase the performance of pathologists in diagnosing squamous lesions in cervical punch and cone biopsies. When using a consecutive p16INK4a-stained slide in conjunction to the H&E-stained slide, interobserver agreement between 6 pathologists improved significantly for both cervical punch and cone biopsies (P < 0.001). For punch biopsies (n = 247), kappa value increased from 0.49 (moderate agreement) to 0.64 indicating substantial agreement, and interobserver agreement for cone biopsies (n = 249) improved from 0.63 (conventional H&E slide reading) to 0.70 when H&E-stained slides were read conjunctively with p16INK4a-stained slides. In comparison to a common consensus diagnosis established by 3 independent experts, 4 pathologists reached an improvement with the conjunctive p16INK4a test, 2 of them showing significantly better agreement (P < 0.001 and P = 0.002, respectively), p16INK4a immunohistochemistry as an adjunct to conventional H&E-stained specimens thus contributes to a more reproducible diagnosis of cervical intraepithelial neoplasia and may be a valuable aid for the interpretation of cervical histology.

Nuclear localization and cytosolic overexpression of LASP-1 correlates with tumor size and nodal-positivity of human breast carcinoma.

BACKGROUND: LIM and SH3 protein 1 (LASP-1), initially identified from human breast cancer, is a specific focal adhesion protein involved in cell proliferation and migration, which was reported to be overexpressed in 8-12 % of human breast cancers and thought to be exclusively located in cytoplasm. METHODS: In the present work we analyzed the cellular and histological expression pattern of LASP-1 and its involvement in biological behavior of human breast cancer through correlation with standard clinicopathological parameters and expression of c-erbB2 (HER-2/neu), estrogen- (ER) and progesterone-receptors (PR). For this purpose immunohistochemical staining intensity and percentage of stained cells were semi-quantitatively rated to define a LASP-1 immunoreactive score (LASP-1-IRS). LASP-1-IRS was determined in 83 cases of invasive ductal breast carcinomas, 25 ductal carcinomas in situ (DCIS) and 18 fibroadenomas. Cellular LASP-1 distribution and expression pattern was visualized by immunofluorescence and confocal microscopy and assessed through separate Western blots of nuclear and cytosol preparations of BT-20, MCF-7, MDA-MB231, and ZR-75/1 breast cancer cells. RESULTS: Statistical analysis revealed that the resulting LASP-1-IRS was significantly higher in invasive carcinomas compared to fibroadenomas (p = 0.0176). Strong cytoplasmatic expression of LASP-1 was detected in 55.4 % of the invasive carcinomas, which correlated significantly with nuclear LASP-1-positivity (p = 0.0014), increased tumor size (p = 0.0159) and rate of nodal-positivity (p = 0.0066). However, levels of LASP-1 expression did not correlate with average age at time point of diagnosis, histological tumor grading, c-erbB2-, ER- or PR-expression. Increased nuclear localization and cytosolic expression of LASP-1 was found in breast cancer with higher tumor stage as well as in rapidly proliferating epidermal basal cells. Confocal microscopy and separate Western blots of cytosolic and nuclear preparations confirmed nuclear localization of LASP-1. CONCLUSION: The current data provide evidence that LASP-1 is not exclusively a cytosolic protein, but is also detectable within the nucleus. Increased expression of LASP-1 in vivo is present in breast carcinomas with higher tumor stage and therefore may be related with worse prognosis concerning patients' overall survival.

Overexpression of transketolase TKTL1 is associated with shorter survival in laryngeal squamous cell carcinomas.

Tumorigenesis involves energy production by aerobic glycolysis ("Warburg effect") in malignant tumors. One of the key enzymes is transketolase. Transketolase, transketolase-like-1 (TKTL1), and transketolase-like-2 are known. Antibodies against TKTL1 exist for immunohistochemical investigations. This study investigated the influence of TKTL1 on survival and metastasizing in 40 laryngeal squamous cell carcinomas (SCCs, T2-T4, 27 metastasized). Staining was assessed by an immunoreactive score (IRS) with values from 0 to 12 in primaries and their nodal metastases. The highest IRS was 8. Normal epithelium did not show an expression. Three SCCs were negative. Advanced SCCs had a higher IRS than lower stages. An IRS>4 was associated with a shorter disease specific survival, independent on the tumor stage in the multivariate analysis. Significant differences between metastasized and non-metastasized SCCs were absent, but poorly differentiated SCCs had a higher IRS in their metastases than moderate differentiated SCCs. TKTL1 overexpression is associated with a more aggressive behavior and shorter survival of laryngeal SCCs. These observations could lead to additional therapeutic options targeting a blocking of the enzyme activity.

Differential diagnosis of laryngeal spindle cell carcinoma and inflammatory myofibroblastic tumor--report of two cases with similar morphology.

BACKGROUND: Spindle cell tumors of the larynx are rare. In some cases, the dignity is difficult to determine. We report two cases of laryngeal spindle cell tumors. CASE PRESENTATION: Case 1 is a spindle cell carcinoma (SPC) in a 55 year-old male patient and case 2 an inflammatory myofibroblastic tumor (IMT) in a 34 year-old female patient. A comprehensive morphological and immunohistochemical analysis was done. Both tumors arose at the vocal folds. Magnified laryngoscopy showed polypoid tumors. After resection, conventional histological investigation revealed spindle cell lesions with similar morphology. We found ulceration, mild atypia, and myxoid stroma. Before immunohistochemistry, the dignity was uncertain. Immunohistochemical investigations led to diagnosis of two distinct tumors with different biological behaviour. Both expressed vimentin. Furthermore, the SPC was positive for pan-cytokeratin AE1/3, CK5/6, and smooth-muscle actin, whereas the IMT reacted with antibodies against ALK-1, and EMA. The proliferation (Ki67) was up to 80% in SPC and 10% in IMT. Other stainings with antibodies against p53, p21, Cyclin D1, or Rb did not result in additional information. After resection, the patient with SPC is free of disease for seven months. The IMT recurred three months after first surgery, but no relapses were found eight months after resurgery. CONCLUSION: Differential diagnosis can be difficult without immunohistochemistry. Therefore, a comprehensive morphological and immunohistochemical analysis is necessary, but markers of cell cycle (apart from the assessment of proliferation) do not help.

Parathyroid-hormone-related-protein-associated hypercalcemia in a patient with CLL-type low-grade leukemic B-cell lymphoma.

Humoral hypercalcemia of malignancy is a common metabolic disturbance associated with solid tumors, but it also occurs in lymphoma patients. Among these, low grade B-cell lymphoma accounts for only few cases, in which secretion of parathyroid hormone-related protein (PTHrP) remains even exceptional. We report the very rare case of a patient with a CLL type low grade leukemic B-cell lymphoma showing PTHrP-related hypercalcemia without evidence of bone lesions. Using immunohistochemistry, we demonstrate the cytoplasmic expression of PTHrP by the lymphoma cells in the bone marrow obtained at the onset of hypercalcemia. We postulate a pathogenetic role of leukemic cell production and secretion of PTHrP in hypercalcemia in low grade leukemic B-cell lymphoma.

Heterogeneous expression of human cathelicidin hCAP18/LL-37 in inflammatory bowel diseases.

BACKGROUND: Inflammatory bowel diseases (IBDs) are characterized by a breakdown of colon epithelial barrier function. Antimicrobial peptides like cathelicidins are molecules of the innate immune system located at epithelial surfaces. Cathelicidins influence microbial growth and inflammation and may play a role in IBD. In this study, the expression of human cathelicidin hCAP18/LL-37 was investigated in the intestinal mucosa from patients suffering from ulcerative colitis or Crohn's disease. METHODS: Biopsy material from colon and ileal mucosa of a total of 89 patients (34 with Crohn's disease, 27 with ulcerative colitis, 28 control patients) was evaluated for cathelicidin expression by real-time reverse-transcriptase polymerase chain reaction and immunohistochemistry. Colon epithelial cells were stimulated in vitro with various cytokines to evaluate mechanisms that influence cathelicidin production. RESULTS: Cathelicidin expression was significantly increased in inflamed and non-inflamed colon mucosa from ulcerative colitis patients compared to non-inflamed control mucosa. In patients with Crohn's disease cathelicidin expression was not changed in inflamed or non-inflamed colon or ileal mucosa independent of NOD2 status. Biopsies evaluated by immunohistochemistry showed epithelial cathelicidin expression in the upper crypt that was diffuse in controls and only basal in IBD patients. Inflammation mediators, alone or in combination with the known cathelicidin inducer butyrate, had no effect on cathelicidin expression in cultured colon cells. CONCLUSIONS: In IBD the colonic expression of human cathelicidin is altered: cathelicidin expression is increased in inflamed and non-inflamed mucosa in patients suffering from ulcerative colitis but not in Crohn's disease. This deficiency may further compromise the antimicrobial barrier in Crohn's disease.

Metastasizing vulvar carcinosarcoma with squamous carcinomatous and leiomyosarcomatous differentiation: genetic evidence of clonal origin.

In this report, we present the first case of a vulvar carcinosarcoma with squamous carcinomatous and leiomyosarcomatous differentiation. Comparative genomic hybridization was used to analyze clonality of the two tumor components. A widely identical pattern of genetic imbalances in the comparative genomic hybridization analysis in both the carcinomatous and the sarcomatous tumor component strongly supported the concept of a bidirectionally differentiated neoplasm. In both tumor components and two lymph node metastases, an amplicon was detected on chromosome 11q12-q13, homing the cyclin D1 gene locus. In contrast, exclusively in the sarcomatoid component, a characteristic amplicon on 12q13-q14 was found. The cytogenetic profile of the lymph node metastases revealed an increase in imbalances compared with the primary tumor. In summary, we found strong indications for a clonal origin of the two tumor components in a vulvar carcinosarcoma and a good correlation of the histological morphology with the pattern of genetic imbalances.

Placenta percreta with subsequent uterine rupture at 15 weeks of gestation after two previous cesarean sections.

A 25-year-old gravida 3 para 2 woman was referred to our hospital at 15 weeks' gestation with an acute abdomen and free fluid in the peritoneal cavity. On admission she was somnolent. She had a history of two cesarean sections. Fetal cardiac activity was detectable by ultrasound preoperatively. Intraoperatively, a lower uterine-segment rupture was identified in the area of the presumed prior uterine incision. The great blood loss with consecutive coagulopathy required an emergency hysterectomy and multiple blood transfusions. The placenta was located on the lower anterior uterine wall. Intervening decidual cells between placenta and maternal scar tissue were absent in the area of the prior uterine incision. Placental villous tissue deeply invaded and perforated the scar tissue. Histological examination revealed a placenta percreta. Placenta percreta with subsequent uterine rupture is a rare but dramatic complication after previous cesarean section. This should be kept in mind as the rate of elective cesarean sections is rising continuously. Our patient recovered completely.

Toll-like receptors TLR4, TLR5 and TLR9 on gastric carcinoma cells: an implication for interaction with Helicobacter pylori.

In the human stomach Toll-like receptors (TLRs) expressed by the gastric epithelium interact with Helicobacter pylori and mediate production of proinflammatory cytokines and chemokines during H. pylori infection. This results in chronic active gastritis, the background from which gastric carcinoma arises via the epithelial precursor lesions, intestinal metaplasia and dysplasia. Therefore, the question is arising whether gastric carcinoma cells are also able to interact with H. pylori. In this study, TLR4, TLR5 and TLR9 expression was investigated on tumor cells of gastric carcinoma and on its precursor lesions, intestinal metaplasia and dysplasia, by immunohistochemistry. Gastric epithelium with intestinal metaplasia (n=10) and dysplasia (n=3) expressed TLR4 and TLR5. TLR4 was strongly expressed by tumor cells of 17 out of 22 and TLR5 by tumor cells of all 22 patients with gastric carcinoma. TLR9, however, was not detectable in intestinal metaplasia or dysplasia and only focally in 6 out of 22 gastric carcinomas. In contrast to H. pylori gastritis, epithelial TLR expression in intestinal metaplasia, dysplasia and gastric carcinoma was diffusely distributed without subcellular polarization as demonstrated by confocal microscopy. This is the first study describing TLR expression on tumor cells of gastric carcinoma and its precursor lesions. Expression of TLRs enables gastric carcinoma cells to interact with H. pylori. As H. pylori can induce gastric carcinoma-promoting factors, such as IL-8, via epithelial TLR expression, TLR expression by gastric carcinoma cells may have a dangerous potential.

Downregulation of CXCR1 and CXCR2 expression on human neutrophils by Helicobacter pylori: a new pathomechanism in H. pylori infection?

In Helicobacter pylori gastritis, neutrophil activation and migration, which play central roles in the pathogenesis of the disease, are regulated by the neutrophil attractant chemokines interleukin 8 (IL-8) and Groalpha, whose secretion is induced by H. pylori. However, the modulation of the corresponding chemokine receptors CXCR1 and CXCR2 on human neutrophils under the influence of H. pylori has not been investigated. Incubation of neutrophils with cag(+) and cag deletion H. pylori strains resulted in a complete downregulation of the CXCR1 and the CXCR2 receptors after 0.5 h, as tested by fluorescence-activated cell sorter analysis, independent of the cag status. Downregulation of CXCR1 and CXCR2 seems to occur via receptor internalization and rapid degradation, as shown by confocal microscopy and immunoblotting. Neither the proinflammatory cytokines IL-8 and tumor necrosis factor alpha produced by the neutrophils themselves nor H. pylori lipopolysaccharide, which are the known regulators of these two chemokine receptors, was responsible for the downregulation. Reverse transcription-PCR analysis showed that CXCR1 and CXCR2 mRNAs of neutrophils were reduced at a later time than the CXCR1 and CXCR2 proteins. Moreover, cag(+) H. pylori strains induced significantly stronger downregulation of CXCR1 and CXCR2 mRNAs than the cag deletion mutant. Therefore, receptor protein and mRNA downregulation seem to be mediated by two independent mechanisms. Data obtained by immunohistochemistry suggested that downmodulation of CXCR1 and CXCR2 on neutrophils may also occur in vivo in the human stomach during H. pylori infection. Downregulation of CXCR1 and CXCR2 expression on neutrophils in H. pylori infection by H. pylori itself may represent a new mechanism of modulating neutrophil migration and activation in the gastric mucosa.

Histone-deacetylase inhibitors induce the cathelicidin LL-37 in gastrointestinal cells.

UNLABELLED: Histone-deacetylase (HDAC) -inhibitors enhance acetylation of core proteins and this is linked to formation of transcriptionally active chromatin in various cells. In this study, the effect of HDAC inhibitors (butyrate, trichostatin A (TSA)) on the expression of the cathelicidin LL-37 in colon, gastric and hepatocellular cells was investigated. METHODS: LL-37 expression was assessed in colon, gastric and hepatocellular cancer cells after treatment with HDAC-inhibitors. In parallel, histone H4 and HMGN2, a non-histone protein, acetylation was evaluated. In addition, the intracellular signalling pathway MEK-ERK was explored. RESULTS: In contrast to normal colon epithelial cells, gastrointestinal cancer cells lacked LL-37 expression. LL-37 was induced following treatment with HDAC-inhibitors in all investigated cell lines. This induction was time-dependent in butyrate-treated cells while TSA exerted a transient effect. Induction of LL-37 by butyrate was paralleled by acetylation of the histone H4 and the non-histone HMGN2. Again, TSA resulted in transient acetylation. Furthermore, inhibition of MEK-ERK blocked HDAC inhibitor-induced LL-37 expression in colonic and gastric cells. CONCLUSIONS: We have previously shown that butyrate induces LL-37 in colon epithelial cells. In the present study, we demonstrate that cathelicidin expression is modulated by HDAC-inhibitors in various gastrointestinal cells including gastric and hepatocellular cells. This is paralleled by changes in the acetylation of distinct core proteins suggesting a common regulatory mechanism of cathelicidin LL-37 regulation in these cells.

PAM-1, a natural human IgM antibody as new tool for detection of breast and prostate precursors.

Early detection and differential analysis of premalignant lesions are very important for both prognosis and therapy of cancer patients. A good source of diagnostic tools is the natural antibody pool of humans. Tumor-specific antibodies can be established by using hybridoma technology. The fully human germline-coded monoclonal IgM antibody PAM-1 was isolated from a patient with a stomach carcinoma. PAM-1 reacts with a post-transcriptionally modified isoform of membrane receptor CFR-1 which is overexpressed on almost all epithelial cancers of all types and origins. The expression of CFR-1/PAM-1 on precancerous stages of breast and prostate cancer was analyzed by immunohistochemistry and compared with normal breast and prostate tissue as well as adenocarcinomas of both. In addition FACS analysis was performed to detect receptor expression on benign and malign prostate cells. 73 different tissue samples of prostate and breast precancerous stages and prostate and breast carcinomas were analysed for CFR-1/PAM-1 expression immunohistochemically. The CFR-1/PAM-1 receptor was expressed on nearly all precancerous stages and carcinomas while normal breast and prostate tissue showed negative results. These results were confirmed by FACS analysis showing a CFR-1/PAM-1 expression only on prostate carcinoma cells but not on benign prostate hyperplasia cells. The unique expression of this new CFR-1/PAM-1 receptor makes the PAM-1 antibody an ideal diagnostic and even therapeutic tool for precancerous and cancerous epithelial lesions of the breast and the prostate.

Cysteine-rich fibroblast growth factor receptor 1, a new marker for precancerous epithelial lesions defined by the human monoclonal antibody PAM-1.

Precancerous epithelial lesions are sites of uncontrolled cellular proliferation, generated by irreversible genetic changes. Not all of these lesions progress to invasive cancer, some may even regress, but early detection of abnormal cells can be crucial for survival of the patient. Diagnosis is mainly performed by using morphological parameters. Proliferation markers can facilitate the analysis, if they show a consistent expression, and distinguish between healthy and malignant cells. The fully human monoclonal IgM antibody PAM-1 was isolated from a patient with stomach carcinoma and binds to a new variant of cysteine-rich fibroblast growth factor receptor 1 (CFR-1). This CFR-1/PAM-1 receptor is expressed on nearly all of the epithelial cancers of every type and origin, but not on healthy tissue. It is also present on precursor lesions found in: Helicobacter pylori-induced gastritis, intestinal metaplasia and dysplasia of the stomach, ulcerative colitis-related dysplasia and adenomas of the colon, Barrett's metaplasia and dysplasia of the esophagus, squamous cell metaplasia and dysplasia of the lung, and cervical intraepithelial neoplasia. The unique, growth-dependent expression of this new CFR-1 isoform makes the PAM-1 antibody an ideal diagnostic tool for the detection of precancerous and cancerous lesions.