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Asian Pacific Journal of Cancer... Jun 2024The alterations of EGFR and HER2/neu as growth factor receptors and the cytoplasmic signal transduction proteins of RAS/RAF/MAP kinases including its end effector...
Evaluation of the Expression EGFR, HER2/NEU and the End Effector ERK of the RAS/RAF/MAP Kinase Pathway in Prostatic Adenocarcinoma for a Possible Role as New Target Therapy.
UNLABELLED
The alterations of EGFR and HER2/neu as growth factor receptors and the cytoplasmic signal transduction proteins of RAS/RAF/MAP kinases including its end effector molecule (ERK) are important in the carcinogenesis of many tumors. The activation of these protooncogenes in prostate cancer is still under investigation. The aim of this work was to study EGFR, HER2- neu, inactive (non-phosphorylated) and active (phosphorylated) ERK expression in prostatic adenocarcinomas in correlation to the clinical and pathological parameters.
METHODS
Immunohistochemistry- using tissue microarrays- for EGFR, HER2/neu, non-phosphorylated, and phosphor-ERK, was performed on tissues from 166 patients- with primary prostatic adenocarcinoma with no prior treatment-. The results of different markers expression were correlated with the clinical and pathological parameters and were analyzed statistically.
RESULTS
The prostatic tissue showed EGFR, HER2 neu, phosphorylated and non-phosphorylated ERK expression in 8.4%, 1.4%, 78.2%, and 83.4% respectively whether low (patchy) or high expression (diffuse). There were no significant correlations found between patient characteristics and expression of the tested markers. The negative immune reactivity for non-phosphorylated ERK and EGFR- was significantly correlated with high tumor stage (p values 0.03 and 0.01, respectively).
CONCLUSION
EGFR and HER2/neu may play a limited role in prostatic adenocarcinoma as they showed positive expression in a limited number of the examined tissues specifically HER2neu. The expression of non-phosphorylated ERK (mostly weak to moderate) and phosphorylated ERK (mostly moderate to strong)- was appreciated in most cases. Thus, we suggest that anti-EGFR drugs may have a limited role in the treatment of castrate-resistant prostate cancer, but anti-MEK/ERK drugs may have more promising role as a target therapy. It is recommended to perform further molecular testing to elucidate the exact mechanism and significance of these markers.
Topics: Humans; Male; Prostatic Neoplasms; ErbB Receptors; Receptor, ErbB-2; Adenocarcinoma; Biomarkers, Tumor; Aged; Middle Aged; Prognosis; Phosphorylation; raf Kinases; Follow-Up Studies; MAP Kinase Signaling System; ras Proteins; Aged, 80 and over; Extracellular Signal-Regulated MAP Kinases; Signal Transduction
PubMed: 38918683
DOI: 10.31557/APJCP.2024.25.6.2193 -
Aktuelle Urologie Jun 2024Prostate cancer is one of the most common cancers in men in Europe. Several classes of agents can be considered for the treatment of metastatic prostate carcinoma, and...
BACKGROUND
Prostate cancer is one of the most common cancers in men in Europe. Several classes of agents can be considered for the treatment of metastatic prostate carcinoma, and their use is supported by extensive guidelines. In the treatment of metastatic castration-resistant prostate cancer (mCRPC), it is currently unclear which sequence of systemic therapies is most effective. Currently approved system therapies in the castration-resistant setting generally include hormone-manipulating agents, taxane-based chemotherapies, radioactive agents, or inhibitiors of DNA repair mechanisms. This study aims to summarize real world data of mCRPC therapy.
METHODS
Retrospectively, 90 mCRPC patients undergoing treatment at the University Hospital Schleswig-Holstein, Lübeck Campus between February 2006 and March 2020 were identified. The patient data were analyzed for their treatment sequence and disease progression. Due to the inclusion period, the mCRPC therapy sequences studied were limited to: Abiraterone, Cabazitaxel, Docetaxel, Enzalutamide, Lutetium-177-PSMA and Radium-223. The analysis includes the therapy sequences and their duration, clinical information of the respective cohort, overall and cancer-specific survival (OS/CSS) as well as time to second-line therapy in relation to the respective first-line therapy.
RESULTS
Approximately two-thirds of patients underwent a true therapy sequence (at least two of the drugs listed above), with this proportion halving by the third line.The majority of patients received the sequence (first/second line) abiraterone/docetaxel (n=13), followed by docetaxel/abiraterone (n=12) and abiraterone/enzalutamid (n=10) and docetaxel/docetaxel (n=8).Within the different docetaxel sequences, first-line (mean 4.7 months ± SD 3.1; median 4.0) and rechallenge (mean 5.3 months ± SD 5.9; median 3.0) therapy durations were the longest. The subjective side effect rate of docetaxel was lower in the second line, so that a better tolerability can be assumed here.The abiraterone/docetaxel sequence was used mainly in patients with metachronous metastases. Among the different sequences of abiraterone, first-line (mean 10.8 months ± SD 10.2; median 9.0) and second-line (mean 10.6 months ± SD 9.0; median 7.0) therapy durations were the longest.The sequence abiraterone/enzalutamide was prescribed mainly to older patients with synchronous metastases. Among the different enzalutamide sequences first-line (mean 9.6 months ± SD 7.1; median 7.0) and rechallenge (mean 11.0 ± SD 0.0; median 11.0) therapy durations were the longest.In contrast, the sequence docetaxel/docetaxel was used mainly in younger patients with a high initial PSA.The evaluation shows a trend that both abiraterone and enzalutamide can account for a survival advantage in the first line.
CONCLUSION
Ultimately, an optimal treatment sequence cannot be confidently derived from these data.However, it was found that only a small proportion of patients underwent fourth- or even fifth-line treatment at all. Thus, the focus on first- and second-line in this study seems reasonable. It could be shown in a trend that docetaxel as first-line therapy seems to be disadvantegous regarding OS as well as CSS when compared to abiraterone or enzalutamide. However, due to the small number of patients in this study, a clear significance cannot be derived. Moreover, the subjectively better tolerability of docetaxel in the second-line setting could provide an impetus for treatment planning in multimorbid elderly patients in the future. The sequence abiraterone/docetaxel may offer a beneficial option for initial mCRPC therapy.
PubMed: 38917849
DOI: 10.1055/a-2295-8720 -
PloS One 2024Prostate stem cell antigen (PSCA) is associated with disease progression, promotion of angiogenesis, invasion, metastasis and immune evasion in cancer. However, its...
Prostate stem cell antigen (PSCA) is associated with disease progression, promotion of angiogenesis, invasion, metastasis and immune evasion in cancer. However, its expression pattern and diagnostic and prognostic potential have not been thoroughly analysed from a pan-cancer perspective. This study aimed to examine the effects of PSCA on the prognosis and inflammatory cell infiltration patterns of various cancer types. We analysed the relationship between PSCA expression and immunological subtypes in tumor microenvironment (TME) and the role of molecular subtypes, potentially promising immune biomarkers and tumour-infiltrating lymphocytes (TILs) in various cancer types, especially lung adenocarcinoma (LUAD). In addition, we investigated the prognostic significance of PSCA expression in LUAD. The co-expression network of PSCA was found to be mainly involved in the regulation of immune responses and antigen processing and expression and was significantly enriched in pathological and substance metabolism-related pathways in cancer. Altogether, this study reveals that PSCA is a promising target for immunotherapy in patients with cancer.
Topics: Humans; Antigens, Neoplasm; Prognosis; Tumor Microenvironment; Lymphocytes, Tumor-Infiltrating; Neoplasm Proteins; GPI-Linked Proteins; Biomarkers, Tumor; Neoplasms; Adenocarcinoma of Lung; Lung Neoplasms; Gene Expression Regulation, Neoplastic; Male
PubMed: 38917176
DOI: 10.1371/journal.pone.0298469 -
Clinical Genitourinary Cancer May 2024Granulomatous prostatitis is a medical condition that may mimic prostate cancer.
BACKGROUND
Granulomatous prostatitis is a medical condition that may mimic prostate cancer.
PURPOSE
Granulomatous prostatitis resulting from BCG-exposure can confound the diagnosis of prostate cancer based on prostate imaging and data system (PI-RADS) classification observed on multiparametric prostate magnetic resonance imaging (mpMRI).
STUDY TYPE, POPULATION, ASSESSMENT AND STATISTICAL TESTS
A cohort study was conducted, enrolling consecutive males at risk for prostate cancer who underwent an mpMRI-targeted prostate biopsy between February 2016 and August 2023. The focus of the study was on prior BCG-exposure as adjuvant treatment for non-muscle-invasive urothelial carcinoma within the 3 years prior the magnetic resonance imaging (MRI). Exclusion criteria were a prior androgen deprivation therapy, prostate surgery or radiation, and BCG-exposure occurring more than 3 years and less than 3 months before the MRI. Chi-square, logistic-regression, statistical association, and homogeneity tests were used.
RESULTS
Total 712 patients, 899 biopsied lesions (218 PI-RADS 3, 521 PI-RADS 4 and 160 PI-RADS 5) and 20 patients with 30 lesions within the BCG-exposed cohort. Chi-square and logistic-regression tests showed an association between PI-RADS with malignancy and significant tumor (ST), considering PI-RADS3 as the reference (OR: 4.9 [95% CI, 3.4-7.1] for PI-RADS4 and OR: 21.7 [95% CI, 12.4-37.8] for PI-RADS5 for malignancy, and OR: 5.3 [95% CI, 3.2-8.7] for PI-RADS4 and OR: 16.5 [95% CI, 9.4-28.9] for PI-RADS5 regarding ST). A statistically significant negative association was demonstrated between malignancy and ST with respect to BCG-exposure (OR: 0.15 [95% CI, 0.06-0.39] and OR: 0.39 [95% CI, 0.15-1.0], respectively). Statistically significant risk-difference for malignancy in patients nonexposed to BCG regarding those exposed was 45% (61.6% vs. 16.7%) for PI-RADS4, and 68.5% (90.7% vs. 22.2%) and 42.7% (64.9% vs. 22.2%) concerning malignancy and ST for PI-RADS5, respectively.
DATA CONCLUSIONS
Granulomatous prostate reaction caused by BCG-exposure acts as confounding factor for prostate MRI interpretation. The risk of malignancy and significant tumor on targeted biopsy to PI-RADS 3, 4 and 5 is notably lower in exposed patients.
PubMed: 38909528
DOI: 10.1016/j.clgc.2024.102130 -
Critical Reviews in Oncology/hematology Jun 2024Genitourinary cancers (GUCs) encompass malignancies affecting the urinary and reproductive systems, including renal cell carcinoma (RCC), urothelial carcinoma (UC), and... (Review)
Review
CONTEXT
Genitourinary cancers (GUCs) encompass malignancies affecting the urinary and reproductive systems, including renal cell carcinoma (RCC), urothelial carcinoma (UC), and prostate cancer (PC). With the rapidly evolving therapeutic domain of these cancers, cutaneous adverse events (AEs) remain among the most observed toxicities.
OBJECTIVE
To explore the dermatologic AEs linked to novel GUC treatments, their underlying pathophysiology, clinical presentations, and risk factors.
EVIDENCE ACQUISITION
A narrative review of the literature from PubMed and Embase databases was conducted. The search strategy included dermatologic/cutaneous adverse events, risk factors, and pathophysiology in conjunction with the following classes of therapies; immune checkpoint inhibitors (ICIs), antiangiogenic therapies, enfortumab vedotin (EV), erdafitinib, and androgen receptor antagonists (ARAs).
EVIDENCE SYNTHESIS
Maculopapular rash, pruritus, and alopecia are present among the five classes of therapies. ICIs demonstrate the highest incidence of severe drug AEs including Steven Johnson syndrome/toxic epidermal necrolysis. Unique cutaneous AEs present with specific therapies including hand-foot skin reaction and subungual splinter hemorrhage with antiangiogenic drugs, stomatitis/mucositis and onycholysis with erdafitinib. Incidence and type of cutaneous AE also differed within therapies in the same class as seen with apalutamide displaying the highest risk of cutaneous AEs within ARAs. Risk factors for development of cutaneous AEs can be general to therapies, or specific, and include age, immune status, BMI, and gender.
CONCLUSIONS
Dermatologic AEs may impact patients' quality of life and increase the tendency to dose reduce, hold or discontinue life-saving therapies, underscoring the need for vigilant monitoring, early recognition, and collaborative management between medical oncologists, pharmacists, dermatologists and other specialists.
PubMed: 38906514
DOI: 10.1016/j.critrevonc.2024.104420 -
The British Journal of Radiology Jul 2023Thyroid cancer is increasing in incidence. Prostate-specific membrane antigen (PSMA) targeted radionuclide imaging and treatment demonstrated remarkable value in...
The value of gallium-68 prostate-specific membrane antigen PET/CT and 2-[18F]fluoro-2-deoxy-D-glucose PET/CT in the detection of thyroid cancer lesions: a prospective head-to-head comparison.
OBJECTIVE
Thyroid cancer is increasing in incidence. Prostate-specific membrane antigen (PSMA) targeted radionuclide imaging and treatment demonstrated remarkable value in prostate cancer patients. Studies have shown that PSMA is also expressed in thyroid cancer. Our purpose is to evaluate the clinical usefulness of [68Ga]Ga-PSMA-11 PET/CT for the diagnosis of thyroid cancer.
METHODS
We enrolled 23 DTC and 17 RAIR-DTC patients prospectively. All patients underwent [68Ga]Ga-PSMA-11 PET/CT and 2-[18F]FDG PET/CT. PSMA expression was determined by immunohistochemistry on histological samples of lymphatic metastasis of 12 patients. We compared the detection rates and semi-quantitative parameters between [68Ga]Ga-PSMA-11PET/CT and 2-[18F]FDG PET/CT.
RESULTS
A total of 72 lesions were detected. Detection rates of DTC and RAIR-DTC by [68Ga]Ga-PSMA-11 PET/CT were lower than those by 2-[18F]FDG PET/CT (60.00% vs. 90.00%, P = .004; 59.38% vs. 96.88%). Compared with DTC, RAIR-DTC had higher semi-quantitative parameters of 2-[18F]FDG PET/CT. There was no significant difference in semi-quantitative parameters of [68Ga]Ga-PSMA-11 PET/CT between DTC and RAIR-DTC. Immunohistochemistry showed a significantly higher PSMA expression for RAIR-DTC than for DTC. However, there was no significant correlation between PSMA expression and SUVmax on 68Ga-PSMA [68Ga]Ga-PSMA-11 PET/CT.
CONCLUSIONS
[68Ga]Ga-PSMA-11 PET/CT can detect thyroid cancer metastases but its detection rate was lower than that of 2-[18F]FDG PET/CT. There was a difference in PSMA expression levels between DTC and RAIR-DTC, but the difference was not reflected on [68Ga]Ga-PSMA-11 PET/CT.
ADVANCES IN KNOWLEDGE
[68Ga]Ga-PSMA-11 PET/CT has potential value in the diagnosis of thyroid cancer. [68Ga]Ga-PSMA-11 PET/CT could screen out patients who may benefit from PSMA-targeted radionuclide therapy.
PubMed: 38904463
DOI: 10.1259/bjr.20230291 -
Frontiers in Genetics 2024
PubMed: 38903750
DOI: 10.3389/fgene.2024.1437556 -
Cureus May 2024Prostate cancer (PC) is one of the leading causes of cancer death among men worldwide. Brain metastases from PC are very rare, often presenting in advanced stages of the...
Prostate cancer (PC) is one of the leading causes of cancer death among men worldwide. Brain metastases from PC are very rare, often presenting in advanced stages of the disease, and are associated with a poor prognosis. Treatment is complex and may involve surgery or radiotherapy. We present the case of a 64-year-old male diagnosed with localized prostate adenocarcinoma, initially treated with pelvic radiotherapy associated with long-term hormonal treatment. While on this hormonal treatment, around one year after radical treatment initiation, he developed bilateral pulmonary metastases, histologically proven to be related to PC, defining a state of metastatic castration-resistant PC. He was asymptomatic and therefore treatment with enzalutamide was initiated. A partial response to the lung lesions was obtained and maintained for more than a year, at which time new mediastinal lymph node metastases were identified. An endobronchial ultrasound biopsy revealed metastases from carcinoma with neuroendocrine differentiation, favoring lung small-cell carcinoma. The patient started chemotherapy with carboplatin and etoposide, with a response. Due to the progression of the mediastinal lymph nodes after eight months, the patient had to undergo chemotherapy again, this time in combination with atezolizumab, with once again partial response. Given the possibility of drug interactions, enzalutamide was suspended during both cycles of chemotherapy and successfully reintroduced afterward. Three months after restarting enzalutamide, he began complaining of headaches. Brain imaging revealed a single frontobasal lesion, without evidence of simultaneous extracerebral progression. Considering the epileptogenic potential of enzalutamide, it was again suspended. The patient underwent surgery and histology revealed metastases of prostate adenocarcinoma, a very rare finding. Systemic re-staging after surgery revealed the progression of cerebral and extra-cerebral disease. The patient is currently proposed for treatment with whole brain radiotherapy and chemotherapy with docetaxel. This case demonstrates the difficulties associated with the diagnosis and treatment of a patient with two distinct neoplasms. Therapy choices were necessarily adjusted because of significant drug interactions. The diagnosis of brain lesions was the last complication, and it proved to be a challenge as it is a rare entity, with optimal management options not being well established.
PubMed: 38903358
DOI: 10.7759/cureus.60728 -
Cureus May 2024Most prostate cancers are adenocarcinomas. However, there is a rare and aggressive subtype known as small cell carcinoma of the prostate (SCCP). This variant of prostate...
Most prostate cancers are adenocarcinomas. However, there is a rare and aggressive subtype known as small cell carcinoma of the prostate (SCCP). This variant of prostate cancer is marked by its distinctive features, including high-grade malignancy, neuroendocrine differentiation, and a unique clinical presentation, often involving metastases. This report details the presentation and management of a 66-year-old African-American male who was originally diagnosed with high-risk adenocarcinoma of the prostate. At initial diagnosis, the patient was suboptimally treated with radiation alone without androgen deprivation therapy (ADT). On re-biopsy several years later, he was found to have localized recurrent disease with transformation into SCCP. The prognosis for SCCP is poor with a mean survival. Patients typically present with metastases, commonly to the brain, liver, bones, or bladder. SCCP after treatment for adenocarcinoma of the prostate is more common than de novo presentation. The amount of neuroendocrine differentiation of SCCP often increases with treatment, particularly after treatment with ADT. This report emphasizes the importance of timely and optimal care when treating prostate cancer and suggests potential consequences that inappropriate treatment or treatment delays may entail.
PubMed: 38903357
DOI: 10.7759/cureus.60790 -
Modern Pathology : An Official Journal... Jun 2024Nephrogenic adenoma is a benign, reactive lesion seen predominantly in the urinary bladder and often associated with an antecedent inflammation, instrumentation, or...
Nephrogenic adenoma is a benign, reactive lesion seen predominantly in the urinary bladder and often associated with an antecedent inflammation, instrumentation, or operative history. Its histopathological diversity can create diagnostic dilemmas and pathologists utilize morphological evaluation along with available immunohistochemical markers to navigate these challenges. Immunohistochemical assays currently do not designate or specify nephrogenic adenoma's potential putative cell of origin. Leveraging single-cell RNA sequencing technology, we nominated a principal cell collecting duct marker, L1 cell adhesion molecule (L1CAM), as a potential biomarker for nephrogenic adenoma. Immunohistochemical characterization revealed L1CAM to be positive in all 35 (100%) patient samples of nephrogenic adenoma; negative expression was seen in the benign urothelium, benign prostatic glands, urothelial carcinoma in situ, prostatic adenocarcinoma, majority of high-grade urothelial carcinoma, and metastatic urothelial carcinoma. In the study, we also utilized single-cell RNA sequencing to nominate a novel compendium of biomarkers specific for proximal tubule, loop of Henle, and distal tubule (including principal and intercalated cells) which can be used to perform nephronal mapping utilizing RNA in situ hybridization and immunohistochemistry technology. Employing this technique on nephrogenic adenoma we found enrichment of both principal cell marker L1CAM and, the proximal tubule types-A and -B cells markers, PDZKI1P1 and PIGR respectively. The cell type markers for the intercalated cell of distal tubules (LINC01187 and FOXI1), and the loop of Henle (UMOD and IRX5), were found to be uniformly absent in nephrogenic adenoma. Overall, our findings show that based on cell type-specific implications of L1CAM expression, the shared expression pattern of L1CAM between distal tubule principal cell (P) cells and nephrogenic adenoma. L1CAM expression will be of potential value in assisting surgical pathologists towards a diagnosis of nephrogenic adenoma in challenging patient samples.
PubMed: 38901674
DOI: 10.1016/j.modpat.2024.100540