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BACKGROUND: ROS1 fusion is a relatively low prevalence (0.6-2.0%) but targetable driver in lung adenocarcinoma (LUAD). Robust and low-cost tests, such as immunohistochemistry (IHC), are desirable to screen for patients potentially harboring this fusion. The aim was to investigate the prevalence of ROS1 fusions in a clinically annotated European stage I-III LUAD cohort using IHC screening with the in vitro diagnostics (IVD)-marked clone SP384, followed by confirmatory molecular analysis in pre-defined subsets. METHODS: Resected LUADs constructed in tissue microarrays, were immunostained for ROS1 expression using SP384 clone in a ready-to-use kit and Ventana immunostainers. After external quality control, analysis was performed by trained pathologists. Staining intensity of at least 2+ (any percentage of tumor cells) was considered IHC positive (ROS1 IHC + ). Subsequently, ROS1 IHC + cases were 1:1:1 matched with IHC0 and IHC1 + cases and subjected to orthogonal ROS1 FISH and RNA-based testing. RESULTS: The prevalence of positive ROS1 expression (ROS1 IHC + ), defined as IHC 2+/3+, was 4 % (35 of 866 LUADs). Twenty-eight ROS1 IHC + cases were analyzed by FISH/RNA-based testing, with only two harboring a confirmed ROS1 gene fusion, corresponding to a lower limit for the prevalence of ROS1 gene fusion of 0.23 %. They represent a 7 % probability of identifying a fusion among ROS1 IHC + cases. Both confirmed cases were among the only four with sufficient material and H-score ≥ 200, leading to a 50 % probability of identifying a ROS1 gene fusion in cases with an H-score considered strongly positive. All matched ROS1 IHC- (IHC0 and IHC1 + ) cases were also found negative by FISH/RNA-based testing, leading to a 100 % probability of lack of ROS1 fusion for ROS1 IHC- cases. CONCLUSIONS: The prevalence of ROS1 fusion in an LUAD stage I-III European cohort was relatively low. ROS1 IHC using SP384 clone is useful for exclusion of ROS1 gene fusion negative cases.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Estadificación de Neoplasias , Proteínas Tirosina Quinasas , Proteínas Proto-Oncogénicas , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/cirugía , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/cirugía , Adenocarcinoma del Pulmón/metabolismo , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Masculino , Femenino , Proteínas Tirosina Quinasas/genética , Proteínas Tirosina Quinasas/metabolismo , Persona de Mediana Edad , Anciano , Inmunohistoquímica , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Europa (Continente) , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Adulto , Hibridación Fluorescente in SituRESUMEN
Granulomatosis with polyangiitis (GPA) is a rare multisystem disease characterized by vasculitis affecting small vessels, resulting in the formation of necrotising granulomata, primarily affecting the lungs, the upper respiratory tract, and kidneys. Almost all patients have upper and lower respiratory involvement; up to 85% of patients with GPA develop kidney disease within two years of diagnosis. Cutaneous, neurological, and ocular manifestations are also seen with varying frequencies. However, cardiac manifestations of the disease are rare and scarcely reported in the literature. Here, we report a case of a 65-year-old female with an initial diagnosis of pulmonary aspergillosis based on the presence of septate hyphae branching at acute angles on lung biopsy and elevated serum galactomannan, who, over the following months, developed a multitude of issues such as myocardial infarction, sterile endocarditis, splenic infarction, and heart block, as well as the challenges faced in establishing a diagnosis and managing its complications.
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Phyllodes tumors are rare biphasic fibroepithelial lesions of the breast and account for 0.3%-0.5% of primary breast tumors. Malignant phyllodes tumor has a 10%-26% risk of distant metastasis. The most common site of metastasis is lungs followed by bone and soft tissue. This is a rare case of a 42-year-old female with a previous history of malignant phyllodes tumor breast. She presented after 10 years with metastases to multiple sites including lung, abdominal wall, retroperitoneum, bone, and brain. These tumors have a poor overall survival. Accurate diagnosis and aggressive management of malignant phyllodes tumors can help in effective treatment at diagnosis and for close follow-up of the patients.
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Neoplasias de la Mama , Neoplasias Pulmonares , Tumor Filoide , Femenino , Humanos , Adulto , Tumor Filoide/diagnóstico , Tumor Filoide/cirugía , Tumor Filoide/patología , Mama/patología , Resultado del Tratamiento , Neoplasias Pulmonares/patología , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapia , Neoplasias de la Mama/patologíaRESUMEN
A woman in her 80s with known diabetes mellitus and bladder cancer presented to her general practitioner (GP) with pain and swelling in her left foot following trauma. Initial radiographs were reported as normal, prompting a diagnosis of a simple sprain and conservative management. Three months later, the patient was referred to the orthopaedic team due to progressively increasing pain and swelling. Repeat X-rays revealed lytic lesions in both the talus and navicular bones; MRI confirmed the presence of a lytic and proliferative defect in the mid-foot, which was reported as acute Charcot arthropathy with superimposed infection. This was also considered the most likely diagnosis when imaging was reviewed in two separate multidisciplinary team) meetings. However, biopsy demonstrated that the cause of the presentation was in fact acrometastasis from urothelial carcinoma, an infrequently described entity.
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Artropatía Neurógena , Carcinoma de Células Transicionales , Diabetes Mellitus , Neoplasias de la Vejiga Urinaria , Femenino , Humanos , Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Pie , Artropatía Neurógena/diagnóstico por imagen , Artropatía Neurógena/etiología , DolorRESUMEN
Endobronchial involvement is a very rare manifestation of Non-Hodgkin's Lymphoma, which if left untreated, may cause airway obstruction and lead to respiratory failure. Only a few cases have been reported in the literature. This aim of this case report is to highlight the importance of having a high index of suspicion of endobronchial lymphoma in patients presenting with endobronchial lesions either in isolation or in conjunction with widespread lymphadenopathy.
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Head and neck squamous cancers are very aggressive tumors often diagnosed in late stages with poor prognosis. HNSCCs are usually treated by a course of radiation (IR) therapy and followed by surgery. These treatment regimens fail to bring a complete response. Molecular signatures in tumors are attributed to this response and an improved understanding of the signaling events could offer new avenues for therapy. Here, we show that P21 activated kinase-1 (PAK1) - an oncogenic signaling serine/threonine kinase, is activated upon exposure to IR and this leads to an accelerated tumorigenic character in HNSCC cells. Our results show that PAK1 is highly expressed in HNSCC cell lines, as compared to normal buccal mucosa cells and when HNSCC cells were exposed to IR, they show activated PAK1 and an aggressive phenotype as determined by in vitro functional assays. PAK1 levels were elevated in HNSCC as compared to adjacent normal oral tissues and our results also show convincing evidence of activated PAK1 in patient tumor samples of post- IR treatment as compared to pre-IR treatment and is associated with poor survival. Pak1 Knockout (KO) clones in HNSCC cells showed that they were more sensitive to IR as compared to wild type (wt) cells. This altered sensitivity to IR was attributed to enhanced DNA damage response modulated by PAK1 in cells. Overall, our results suggest that PAK1 expression in HNSCC could be a critical determinant in IR therapy response and silencing PAK1 is likely to be a treatment modality to improve clinical outcomes.
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Neoplasias de Cabeza y Cuello , Quinasas p21 Activadas , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello , Quinasas p21 Activadas/genética , Línea Celular Tumoral , Radiación Ionizante , Neoplasias de Cabeza y Cuello/radioterapiaRESUMEN
Nodular hidradenoma is a rare skin adnexal tumor of eccrine differentiation with predominant site being scalp and axillae. Due to its variable locations and unusual clinical presentation and no definite radiological criteria, histopathology seems to be the mainstay in diagnosing these tumors. Most of the lesions present as a cystic swelling and was clinically thought to be a sebaceous cyst/metastasis/carcinoma/sarcoma. In our study, we have included 37 cases and compared its varied clinical and radiological presentation.
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The molecular basis of reduced susceptibility to amphotericin B (rs-AMB) among any yeasts is poorly defined. Genetic alterations in genes involved in ergosterol biosynthesis and total cell sterols were investigated among clinical Candida kefyr isolates. C. kefyr isolates (n = 81) obtained from 74 patients in Kuwait and identified by phenotypic and molecular methods were analyzed. An Etest was initially used to identify isolates with rs-AMB. Specific mutations in ERG2 and ERG6 involved in ergosterol biosynthesis were detected by PCR sequencing. Twelve selected isolates were also tested by the SensiTitre Yeast One (SYO), and total cell sterols were evaluated by gas chromatography-mass spectrometry and ERG3 and ERG11 sequencing. Eight isolates from 8 patients showed rs-AMB by Etest, including 2 isolates with additional resistance to fluconazole or to all three antifungals. SYO correctly identified 8 of 8 rs-AMB isolates. A nonsynonymous mutation in ERG2 was detected in 6 of 8 rs-AMB isolates but also in 3 of 73 isolates with a wild-type AMB pattern. One rs-AMB isolate contained a deletion (frameshift) mutation in ERG2. One or more nonsynonymous mutations was detected in ERG6 in 11 of 81 isolates with the rs-AMB or wild-type AMB pattern. Among 12 selected isolates, 2 and 2 isolates contained a nonsynonymous mutation(s) in ERG3 and ERG11, respectively. Ergosterol was undetectable in 7 of 8 rs-AMB isolates, and the total cell sterol profiles were consistent with loss of ERG2 function in 6 rs-AMB isolates and loss of ERG3 activity in another rs-AMB isolate. Our data showed that ERG2 is a major target conferring rs-AMB in clinical C. kefyr isolates. IMPORTANCE Some yeast species exhibit intrinsic resistance or rapidly acquire resistance to azole antifungals. Despite >50 years of clinical use, resistance to amphotericin B (AMB) among yeast species has been extremely rarely reported until recently. Reduced susceptibility to AMB (rs-AMB) among yeast species is, therefore, a matter of serious concern due to the availability of only four classes of antifungal drugs. Recent studies in Candida glabrata, Candida lusitaniae, and Candida auris have identified ERG genes involved in ergosterol biosynthesis as the major targets conferring rs-AMB. The results of this study also show that nonsynonymous mutations in ERG2 impair its function, abolish ergosterol from C. kefyr, and confer rs-AMB. Thus, rapid detection of rs-AMB among clinical isolates will help in proper management of invasive C. kefyr infections.
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Anfotericina B , Antifúngicos , Humanos , Anfotericina B/farmacología , Antifúngicos/farmacología , Esteroles , Mutación , ErgosterolRESUMEN
Uterine mesenchymal tumors are a heterogeneous group of neoplasms that can be diagnostically challenging. Thorough investigations and histopathological findings are highly significant to arrive at the correct diagnosis, thus ensuring appropriate and prompt treatment to the patient. Leiomyosarcoma (LMS) is an uncommon uterine malignancy, which arises from the smooth muscle of the uterine wall. They usually present in postmenopausal women with abnormal uterine bleeding. It follows an aggressive clinical course with an extremely poor prognosis. Surgical management followed by adjuvant chemotherapy is usually the treatment for such cases. Here, we report the case of a 57-year-old menopausal female who presented with a large abdominal swelling that was seen infiltrating the adjacent structures. On resection and histopathological evaluation, a diagnosis of epithelioid LMS was made, which was confirmed by immunohistochemistry.
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Leiomiosarcoma , Femenino , Humanos , Persona de Mediana Edad , Leiomiosarcoma/diagnóstico , Leiomiosarcoma/terapia , Músculo Liso , Quimioterapia Adyuvante , Menopausia , ÚteroRESUMEN
AIMS: Cancer diagnostics have been evolving rapidly. In England, the new National Health Service Genomic Medicine Service (GMS) provides centralised access to genomic testing via seven regional Genomic Laboratory Hubs. The PATHways survey aimed to capture pathologists' experience with current diagnostic pathways and opportunities for optimisation to ensure equitable and timely access to biomarker testing. METHODS: A nationwide survey was conducted with consultant pathologists from regional laboratories, via direct interviews based on a structured questionnaire. Descriptive analysis of responses was undertaken using quantitative and qualitative methods. RESULTS: Fifteen regional centres completed the survey covering a median population size of 2.5 (1.9-3.6) million (each for n=12). The median estimated turnaround time (calendar days) for standard molecular markers in melanoma, breast and lung cancers ranged from 2 to 3 days by immunohistochemistry (excluding NTRKfus in breast and lung cancers, and PD-L1 in melanoma) and 6-15 days by real-time-PCR (excluding KIT for melanoma), to 17.5-24.5 days by next-generation sequencing (excluding PIK3CA for breast cancer). Tests were mainly initiated by pathologists and oncologists. All respondents discussed the results at multidisciplinary team (MDT) meetings. The GMS roll-out was perceived to have high impact on services by 53% of respondents, citing logistical and technical issues. Enhanced education on new pathways, tissue requirements, report interpretation, providing patient information and best practice sharing was suggested for pathologists and other MDT members. CONCLUSION: Our survey highlighted the role of regional pathology within the evolving diagnostic landscape in England. Notable recommendations included improved communication and education, active stakeholder engagement, and tackling informatics barriers.
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Inverse globe retraction syndrome is a rare ocular motility disorder characterized by limited abduction, with globe retraction and up- or downshoots on attempted abduction, differentiating it from globe retraction due to Duane retraction syndrome, seen on attempted adduction. It can be congenital or acquired. We report the case of a 3-year-old girl who presented with classical features of inverse globe retraction syndrome secondary to an underlying orbital tumor involving the medial rectus muscle. Incisional biopsy confirmed the diagnosis of a leiomyoma. At 10 months' follow-up, vision, ocular alignment, and ocular motility had improved.
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Síndrome de Retracción de Duane , Leiomioma , Neoplasias Orbitales , Femenino , Humanos , Preescolar , Síndrome de Retracción de Duane/diagnóstico , Enfermedades Raras , Neoplasias Orbitales/complicaciones , Neoplasias Orbitales/diagnóstico , Neoplasias Orbitales/cirugía , Movimientos Oculares , Músculos Oculomotores/cirugía , Leiomioma/complicaciones , Leiomioma/diagnóstico , Leiomioma/cirugíaRESUMEN
Invasive fungal infections caused by non-albicans Candida species are increasingly reported. Recent advances in diagnostic and molecular tools enabled better identification and detection of emerging pathogenic yeasts. The Candida haemulonii species complex accommodates several rare and recently described pathogenic species, C. duobushaemulonii, C. pseudohaemulonii, C. vulturna, and the most notorious example is the outbreak-causing multi-drug resistant member C. auris. Here, we describe a new clinically relevant yeast isolated from geographically distinct regions, representing the proposed novel species C. khanbhai, a member of the C. haemulonii species complex. Moreover, several members of the C. haemulonii species complex were observed to be invalidly described, including the clinically relevant species C. auris and C. vulturna. Hence, the opportunity was taken to correct this here, formally validating the names of C. auris, C. chanthaburiensis, C. konsanensis, C. metrosideri, C. ohialehuae, and C. vulturna.
Although C. albicans remains the major pathogenic yeast, other previously rare or even novel species are on the rise in the clinic. The most notorious example is the rapid global emergence of multidrug-resistant C. auris. Here we describe its novel sibling species C. khanbhai.
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Candidiasis , Infecciones Fúngicas Invasoras , Animales , Candidiasis/microbiología , Candidiasis/veterinaria , Saccharomyces cerevisiae , Candida/genética , Infecciones Fúngicas Invasoras/veterinaria , AntifúngicosRESUMEN
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is the predominant type of esophageal cancer in the Asian belt. These cancers show poor prognosis with an overall 5-year survival rate less than 19%. Exploring new molecular therapeutic targets such as epidermal growth factor receptor (EGFR) could be the corner stone of new curative treatment. The present study was done to analyze the overexpression of EGFR in different grades of ESCC and explore its role as a diagnostic and theranostic marker in ESCC. METHODS: In this retrospective study, 50 formalin-fixed paraffin-embedded blocks of ESCCs diagnosed from 2014 to 2019 were retrieved. The biopsies were subjected to immunohistochemistry staining of EGFR. The intensity of the membrane staining was reviewed and scored. Compared with various intrinsic and extrinsic factors using Chi-square test, scores more than 2+ were considered as overexpression. RESULTS: Majority (84%) specimens demonstrated overexpression of EGFR where high-grade ESCCs had greater overexpression rates compared to low-grade ESCC (P < 0.05). CONCLUSION: By targeting the EGFR molecules, anti-EGFR drugs could block their signals and stop the growth and spread of ESCCs especially high-grade tumors while harming the normal cells as little as possible. A clinical trial using anti-EGFR monoclonal antibodies will help in the long run to develop immunotherapy drugs.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/terapia , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Estudios Retrospectivos , Receptores ErbB/genética , Receptores ErbB/metabolismoRESUMEN
Many rare yeasts are emerging as pathogens, causing invasive infections in susceptible hosts that are associated with poor clinical outcome. Here, we describe the first and fatal case of Lodderomyces elongisporus fungemia in a premature, extremely low-birth-weight neonate after spontaneous vaginal delivery. The bloodstream isolate was identified as C. parapsilosis by the VITEK 2 yeast identification system and as L. elongisporus by PCR-sequencing of the internal transcribed spacer (ITS) region of ribosomal DNA. Antifungal susceptibility testing data for the isolate, performed by the broth microdilution-based MICRONAUT-AM assay, showed susceptibility to all nine antifungal drugs tested. Despite the initiation of treatment with liposomal amphotericin B, the patient died on the same day that the blood culture yielded yeast growth. This is the first report of L. elongisporus bloodstream infection in a neonate as the previous nine cases reported in the literature occurred in adult patients. The crude mortality rate for invasive L. elongisporus infection is 50%, as only 5 of 10 patients survived.
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Introduction: Reduced expression of E-cadherin, an intercellular junction protein, is associated with differentiation and metastasis of multiple cancers, including colorectal cancer. Aim: To investigate the utility of the immunohistochemistry of E-cadherin as a prognostic marker for colorectal cancer (CRC). Material and methods: Immunohistochemical analysis for E-cadherin was performed on 100 paraffin blocks retrieved from resected specimens of CRC patients. The collected data were statistically analysed. Results: Among the 100 patients, men comprised 58% and the majority had tumour size of 5-10 cm (55%). Grade II CRC was more common (74%) than grade I and III (13% each). The correlation of E-cadherin expression with lymph node involvement was statistically significant, as revealed by p-value < 0.01, with about 27% in N1 and 13% in N2 stage. E-cadherin expression was significantly correlated with tumour differentiation pattern (p < 0.01), wherein out of 13 poorly differentiated carcinomas, 38.5% and 30.5% of samples showed negative and weak E-cadherin staining, respectively. Conclusions: Furthermore, a shift from membranous E-cadherin staining in normal cells to cytoplasmic and mixed staining was observed in cancer cells. The study indicates that immunohistochemical E-cadherin expression has prognostic value, as revealed by its loss of expression in poorly differentiated cells and lymph node metastasis.
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Candida auris is an emerging yeast pathogen that has recently caused major outbreaks in healthcare facilities worldwide. Clinical C. auris isolates are usually resistant to fluconazole and readily develop resistance to echinocandins and amphotericin B (AMB) during treatment. We describe here an interesting case of C. auris infection in an immunocompromised patient who had previously received AMB and caspofungin treatment. Subsequently, C. auris was isolated from tracheal (tracheostomy) secretions and twice from urine and all three isolates were susceptible to AMB and micafungin. The patient received a combination therapy with AMB and caspofungin. Although the C. auris was cleared from the urine, the patient subsequently developed breakthrough candidemia and the bloodstream isolate exhibited a reduced susceptibility to micafungin and also showed the presence of a novel (S639T) mutation in hotspot-1 of FKS1. Interestingly, C. auris from the tracheal (tracheostomy) secretions recovered one and four days later exhibited a reduced susceptibility to micafungin and S639Y and S639T mutations in hotspot-1 of FKS1, respectively. Although the treatment was changed to voriconazole, the patient expired. Our case highlights a novel FKS1 mutation and the problems clinicians are facing to treat invasive C. auris infections due to inherent or developing resistance to multiple antifungal drugs and limited antifungal armamentarium.
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INTRODUCTION: Imaging-guided breast tissue biopsy has become an acceptable alternative to open surgical biopsy for nonpalpable breast lesions. Discussion of abnormal results of the correlation between imaging and pathological findings can be very challenging as it can assist in decision-making with regard to the further treatment options by arriving at a comprehensive diagnosis. MATERIALS AND METHODS: This was a retrospective study. Radiological data from imaging-guided breast biopsies of 500 patients during a 6-year period was collected and classified by a specialist radiologist as per the BI-RADS format. Histopathology reports were studied and discordance analyzed. RESULTS: A total of 500 cases were reviewed. Approximately 33% (168) cases fell into the BI-RADS 3 category, 24.4% (122) into the BI-RADS 4, and 37% (187) into BI-RADS 5 categories. Approximately 50% (n = 250) cases were benign, 2.6% (13) belonged to the high-risk category, and 47.4% (237) were malignant. The number of discordant cases was 12 (2.4%), mostly due to technical factors. Sensitivity of biopsies to detect malignancy was 85%, specificity was 96%, and accuracy of biopsy in diagnosing cancer was 90%. DISCUSSION: The "triple assessment" is the most sensitive method for detecting early breast cancer. An effective communication pathway must be established between a clinician, radiologist, and pathologist for surgical excision in discordance as it carries a high prevalence of carcinoma in these lesions. CONCLUSION: In discordant cases, either due to abnormal results of imaging or of abnormal pathological findings, the final decision is based on two concordant findings, out of the three parameters. This involves a multidisciplinary breast conference and an active participation by the pathologist.
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Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Mama/patología , Técnicas Histológicas/normas , Mamografía/normas , Adulto , Biopsia , Mama/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/patología , Femenino , Humanos , Mamografía/estadística & datos numéricos , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
Precocious puberty (PP) in pediatric office practice is challenging as the cause varies from benign to malignant conditions. Adrenocortical tumors are rare in childhood and pseudo-precocious puberty is the most common clinical presentation in children. We report a case of a 5-year-old boy who presented with features of abdominal distention and virilization, and his abdominal magnetic resonance imaging (MRI) revealed an adrenal tumor which was confirmed as adrenocortical carcinoma by biopsy. This case report highlights the importance of the awareness among general practioners and pediatricians to rule out adrenocortical tumors while evaluating a child with PP.
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The inflammatory tumor microenvironment has been implicated as a major player fueling tumor progression and an enabling characteristic of cancer, proline, glutamic acid, and leucine-rich protein 1 (PELP1) is a novel nuclear receptor coregulator that signals across diverse signaling networks, and its expression is altered in several cancers. However, investigations to find the role of PELP1 in inflammation-driven oncogenesis are limited. Molecular studies here, utilizing macrophage cell lines and animal models upon stimulation with lipopolysaccharide (LPS) or necrotic cells, showed that PELP1 is an inflammation-inducible gene. Studies on the PELP1 promoter and its mutant identified potential binding of c-Rel, an NF-κB transcription factor subunit, to PELP1 promoter upon LPS stimulation in macrophages. Recruitment of c-Rel onto the PELP1 promoter was validated by chromatin immunoprecipitation, further confirming LPS mediated PELP1 expression through c-Rel-specific transcriptional regulation. Macrophages that overexpress PELP1 induces granulocyte-macrophage colony-stimulating factor secretion, which mediates cancer progression in a paracrine manner. Results from preclinical studies with normal-inflammatory-tumor progression models demonstrated a progressive increase in the PELP1 expression, supporting this link between inflammation and cancer. In addition, animal studies demonstrated the connection of PELP1 in inflammation-directed cancer progression. Taken together, our findings provide the first report on c-Rel-specific transcriptional regulation of PELP1 in inflammation and possible granulocyte-macrophage colony-stimulating factor-mediated transformation potential of activated macrophages on epithelial cells in the inflammatory tumor microenvironment, reiterating the link between PELP1 and inflammation-induced oncogenesis. Understanding the regulatory mechanisms of PELP1 may help in designing better therapeutics to cure various inflammation-associated malignancies.