High Molecular Cytokeratin Research Articles

MP14-02 DEVELOPMENT OF A PORCINE MODEL OF BLADDER CANCER USING THE ONCOPIG

You have accessJournal of UrologyCME1 Apr 2023MP14-02 DEVELOPMENT OF A PORCINE MODEL OF BLADDER CANCER USING THE ONCOPIG Andreas Aulitzky, Rand Wilcox Vanden Berg, Kwanghee Kim, Hikmat Al-Ahmadie, Sebastien Monette, and Jonathan A. Coleman Andreas AulitzkyAndreas Aulitzky More articles by this author , Rand Wilcox Vanden BergRand Wilcox Vanden Berg More articles by this author , Kwanghee KimKwanghee Kim More articles by this author , Hikmat Al-AhmadieHikmat Al-Ahmadie More articles by this author , Sebastien MonetteSebastien Monette More articles by this author , and Jonathan A. ColemanJonathan A. Coleman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003234.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Large animal cancer models have potential to improve and accelerate the development of new treatment modalities but few exist. Oncopigs (OPG) are particularly suitable due to their similarities to humans. We sought to develop a urothelial tumor model using the oncopig cancer model (OCM: University of Illinois Cancer Center). The OCM carries two mutations (KRASG12D and TP53R167H) which can be induced by exposure to a buffered Adeno Virus Cre solution (bAdCre). Three procedures (P1, P2, P3) were devised and investigated. METHODS: Eight OPGs underwent tumor inoculation. In P1, bAdCre with plant starch (n=3) was injected submucosally at 3 distinct locations in the bladder wall. In P2 the urothelium was denuded in 3 locations followed by bAdCre instillation (n=4). In P3 bAdCre was instilled combined with N-Dodecyl- β-D-Maltoside (DDM), an alkyl disaccharide and polar surfactant that enhances virus transfection in the bladder, with intact urothelium (n=1). Serial imaging, cystoscopies and blood draws were performed until sacrifice at 3 timepoints (days: 14, 21, 28). Tumor characteristics were assessed by necropsy and histopathological examination of the entire tumor tissue. RESULTS: In total, 7/8 (87.5%) OPGs grew bladder tumors. Histopathological examination revealed 2 different tumor types: neoplastic tumors (NT) and inflammatory tumors (IT). Using P1, 3 OPGs developed IT (3/3). 2 OPGs in 2 locations (2/3) and 1 in 1 location (1/3). In P2, 3/4 OPGs grew tumors. 1 OPG in all 3 locations, all 3 were NTs (3/3) (Figure 1 a), 1 OPG in 2 locations (2/3), both NTs and 1 OPG in 1 location (1/3), an IT. In P3 1 NT developed (1/1). All tumors showed muscle invasive growth. P3 showed the most superficial lesion after 21 days (pT2a). In P1, 2 pigs had pT3 tumors after 21 and 28 days. No complications were observed. Based on the histological (Figure 1 b: H&E), multiple immunohistochemical findings (e.g.: Figure 1 c: high molecular cytokeratins 34Be12; Figure 1 d: P53) and the growth pattern, NT were diagnosed as urothelial cell carcinomas, sarcomatoid variant. CONCLUSIONS: This is the first description of bladder tumor development in a porcine model using the OCM. We were able to create neoplastic tumors in a short period of time. The model is reproducible and neoplastic lesions show urothelial origin with sarcomatoid transformation. Source of Funding: MSKCC Sidney Kimmel Center for Urologic Cancers © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e182 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Andreas Aulitzky More articles by this author Rand Wilcox Vanden Berg More articles by this author Kwanghee Kim More articles by this author Hikmat Al-Ahmadie More articles by this author Sebastien Monette More articles by this author Jonathan A. Coleman More articles by this author Expand All Advertisement PDF downloadLoading ...

Prostate cancer diagnosis: an immunological aspects

Introduction.Contemporary diagnosis of prostate cancer is crucial to the patient’s further fate. Difficulties in the histological verification of the final diagnosis and false-negative results of biopsy research are often associated with the similarity of the prostate adenocarcinoma`s micromorphological picture and its benign lesions.Purpose of the study.Comprehending the possibilities of immunohistochemical identification of tumor cells and the basal epithelial layer of prostate glandular structures in prostate cancer suspected cases.Materials and methods.A biopsy material was taken from 134 patients. Prostate adenocarcinoma was verified by routine histological examination in 72 samples, in 62 samples there were no signs of malignant transformation. Subsequently, immunohistochemical analysis of biopsy specimens was performed using antibodies to α-methylacyl-CoA racemase, nuclear p63 protein and high-molecular cytokeratin.Results.The AMACR-positive reaction of malignant cells and a negative reaction of the basal epithelium to nuclear p63 protein antibodies and high-molecular cytokeratin were detected during prostate adenocarcinoma.Conclusion.If prostate cancer is suspected, immunohistochemical assays with monoclonal antibodies to AMACR, p63 and high-molecular cytokeratin greatly facilitate the detection of adenocarcinoma.

DIAGNOSTIC INFORMATIVITY OF IMMUNOHISTOCHEMICAL BIOMARKERS IN CONDUCTING PRIVATIC PATHOLOGICAL AND ANATOMICAL RESEARCH OF PROSTATE CANCER

The results of an in vivo pathoanatomical differential diagnosis of primary acinar adenocarcinoma of the prostate and benign lesions of the prostate gland were analyzed using a transrectal biopsy of the prostate gland using an optimized panel of antibodies to high-molecular cytokeratins (clone 34E12), protein P63, AMACR, PSA and/or PSRA. The greatest diagnostic informativity of the basal cell differentiation marker of the columnar prostate epithelial cells was shown. The use of this set of biomarkers contributes to the establishment of a correct diagnosis and, in addition to the routine morphological examination of the biopsy material, can be recommended for carrying out an intravital pathologic anatomic differential diagnosis of prostate cancer.

Paraganglioma-Like Medullary Thyroid Carcinoma: A Rare Entity

The wide variety of rare histologic variants of medullary thyroid carcinoma (MTC) may make the differential diagnosis difficult. Pathologic examination of the resected specimen will not always be able to confirm the diagnosis, leaving the surgeon with an uncertainty as to what type of resection is best for the patient. The following report describes the case of a 58-year-old man with the rare diagnosis of paraganglioma-like MTC. The patient presented with markedly elevated calcitonin (CT) and carcinoembryonic antigen (CEA) levels. A 1-cm tumor was detected in the right lobe of the thyroid. Based on the clinical diagnosis of MTC, we performed a total thyroidectomy with lymphadenectomy of the central and right lateral compartments. Paraffin sections of the resected specimen were stained with hematoxylin and eosin (H&E) and immunohistochemically characterized using antibodies to CT, CEA, chromogranin A, thyroglobulin, synaptophysin, sustentacular cells (SCs), low- and high-molecular cytokeratins (CK 5/6, 7, 18, 20), epidermal growth factor-receptor (EGFR), thyroid transcription factor-1 (TTF-1), bcl-2, Melan A, C-kit, neuron-specific enolase (NSE), and galectin-3. The patient's blood and tumor tissue were examined for mutations in the RET-protooncogene. H&E staining of both frozen and permanent sections was unable to differentiate benign from malignant tissue. Typical morphologic characteristics for MTC were completely absent. Only the additional finding of positivity for synaptophysin and numerous SC cells visible in-between neoplastic cells made the diagnosis of paraganglioma-like MTC possible. Sequencing of the RET proto-oncogene revealed no mutations. There are subgroups of MTC that present clinically similar to classic MTC, but in which missing typical morphologic characteristics make histopathology diagnosis difficult. In these cases, diagnosis, operative decisions, and follow-up strategies should be based on preoperative biochemical markers, imaging findings, and clinical parameters in accordance to the guidelines for classic MTC.

Trichoblastoma with Apocrine and Sebaceous Differentiation

Trichoblastoma is a rare, benign tumor that differentiates toward the hair germ, the embryonic precursor of a hair follicle. Several cases of trichoblastoma showed multiple differentiation toward more than one type of adnexal structure. We report a case of a trichoblastoma, which had developed on the scalp as a solitary 1-cm nodule 3 years ago. A histologic examination indicated that the specimen had features of multiple differentiation. In particular, there were occasional foci of decapitation secretion, as well as cells with web-like and bubbly cytoplasm suggesting seboblasts, and a sebaceous duct-like structure. In addition, there were occasional germinative cells in the palisade, and scattered hair papilla-like structures showing follicular differentiation. An immunohistochemical study showed that the neoplasm, or areas in it, stained positive for low molecular cytokeratin, high molecular cytokeratin, EMA, S-100, and GCDFP-15. This is an unusual case of a trichoblastoma with apocrine and sebaceous differentiation.

Correlation of high-molecular cytokeratin in tissue of prostatic cancer with gleason score and PSA

The absence of basal cell layer of prostatic acini containing high-molecular cytokeratin, which is immunohistochemically detected by monoclonal antibody 34betaE12, is an essential diagnostic characteristic of prostatic cancer. The absence of immunohistochemical reaction in 3 or more pseudoglandular structures of prostatic tissue indicates malignant process. The percentage of immunohistochemically completely negative glandular structures was determined by semiquantitative measurement in tissue specimens obtained by TRUS biopsy of the prostate, and it was correlated with serum PSA concentration and Gleason score. The increase of percentage of glandular prostatic formations completely negative to high-molecular cytokeratin detected by 34betaE12 led to simultaneous rise of mean value of Gleason prostatic cancer score (p < 0.001) as well as the average serum PSA concentration in subjects (p < 0.05).

The diagnostic value of 34 betaE 12 in differential diagnosis of benign and malignant mammary lesions

To determine the differential diagnostic value of high molecular cytokeratin 34betaE12 as a benign marker in mammary lesions. 90 cases (30 benign non-proliferative diseases, 20 benign proliferative diseases, 10 intraductal carcinomas and 30 invasive carcinomas) were collected, all of which had undergone fine needle aspiration cytology (FNAC) examination and a follow-up operation. Immunohistochemical staining was performed using monoclonal antibodies against 34betaE12 on FNAC smears and the follow-up paraffin sections. SPSS 10.0 software was applied to analyze the differential diagnostic value of 34betaE12 in benign and malignant mammary lesions. (1) No significant difference was found in the expression of 34betaE12 between benign non-proliferative and proliferative disease. (2) A significant difference was found between the expression of 34betaE12 in mammary benign disease and mammary carcinoma. 66.7% and 66.3% of the carcinoma cases showed either lack of 34betaE12 expression or had only a few isolated 1+ cells which were cytoplasmic positive for 34betaE12 immunoreaction on FNAC smear and paraffin section respectively. The remaining 33% of cases having 2+ to 3+ cells mainly displayed cytoplasmic granular positive reaction rather than strong membranous and cytoplasmic positive reaction as benign lesions. In contrast with carcinoma, most benign lesions showed strong immunoreaction of 2+ to 3+ and especially exhibited complete strong membranous and cytoplasmic positive reaction on paraffin section, their positive expressive character differed from those of carcinoma. The positive rates on FNAC smear and paraffin section were 100% and 78% respectively. (3) Certain types of intraductal carcinoma, including low grade cribriform, papillary and solid type either lacked 34betaE12 expression or revealed a few isolated 1+ cells with cytoplasmic positivity for 34betaE12 immunoreaction. Pronounced immunoreaction of 3+ was only seen in high grade comedotype intraductal carcinoma. 34betaE12 may serve as a marker of benign mammary disease for differential diagnosis. When there is a total or predominant lack of 34betaE12 expression, the possibility of carcinoma should be strongly considered. If 34betaE12 is expressed diffusely in the suspicious area with a strong membranous staining in particular, a benign proliferative process rather than carcinoma must be considered.

Prostatic tissue in mature cystic teratomas of the ovary: a report of four cases, including one with features of prostatic adenocarcinoma, and cytogenetic studies.

Four cases of mature cystic teratoma that contained prostatic tissue are reported. The ovarian tumors occurred in patients from 17 to 38 (mean 31) years of age and had no unusual clinical or gross aspects. The microscopic findings for the most part were typical of a mature cystic teratoma, but they also contained foci of prostatic tissue that ranged from 0.2 to 1.9 cm in greatest dimension. In these areas there was a lobular arrangement of medium-sized acini lined by cuboidal to columnar cells with pale cytoplasm and round nuclei with inconspicuous nucleoli except focally in one case as noted below. Basal cells were seen focally. The prostatic acini lay in a paucicellular fibromuscular stroma. In two cases thick layers of disorganized smooth muscle covered by transitional-like pseudostratified epithelium, resulting in an appearance resembling fetal bladder wall, were present next to the prostatic glands. One tumor also contained prostatic-type acini, which haphazardly infiltrated the stroma over an area approximately 5 mm in maximal dimension. The acini, a few of which contained intraluminal flocculent eosinophilic material, were lined by cells with eosinophilic to amphophilic focally granular cytoplasm and had nuclei that were enlarged compared with the benign-appearing, prostatic-type acini in the four cases and had focally prominent nucleoli. Basal cells were not identified in these infiltrating glands. Grading this focus according to the approach in the prostate, the morphology was that of a Gleason grade 3 of 5 adenocarcinoma. Immunohistochemical stains of the putative prostatic epithelial cells confirmed their nature by showing immunoreactivity for prostatic-specific antigen in the lining epithelial cells in all four cases and for prostatic-specific acid phosphatase in the one case tested. The high molecular cytokeratin stain, 34betaE12, highlighted basal cells to a variable extent in the three cases containing only benign prostatic tissue. Material was not available to immunostain for basal cells in the case with carcinoma. Cytogenetic studies were performed in two cases and showed that the great majority of the nuclei of the nonprostatic and prostatic tissue had an XX karyotype but from 3% to 5% of the nuclei displayed trisomy for the X chromosome. A small number of cases of prostatic tissue in ovarian teratomas have previously been documented but none had morphologic features of carcinoma.

Binding of antibodies against high and low molecular weight cytokeratin proteins in the human placenta with special reference to infarcts, proliferation and differentiation processes.

Recent immunocytochemical studies have shown that placental villous trophoblasts contain the high molecular weight cytokeratin (CK) proteins 5/6 and 17. In the case of CK 17, trophoblastic immunostaining was positive in villi covered by fibrinoid. CKs 5/6 and 17 are expressed by hyperproliferative cells. The aim of this investigation was to examine the location of these CKs in placental infarcts, known to be demarcated by fibrinoid and hyperproliferative trophoblasts. The results were compared with those obtained by immunostaining against Ki-67, tenascin and alpha 1-, alpha 6- and beta 1-integrins, which are involved in cell proliferation, differentiation and regenerative processes. Furthermore, the expression of the single CKs 7, 8, 10, 13, 14, 18 and 19 was investigated by immunocytochemistry and immunoblotting. While low and high molecular weight CKs were present in villous and extravillous trophoblasts, only low molecular weight CKs were detected in vascular and extravascular placental smooth muscle cells. Placental infarcts revealed different immunoreactivities in the infarct margin and centre: high molecular CKs, tenascin, Ki-67 and oncofoetal fibronectin predominated in the infarct margin, low molecular CKs, fibrin and integrins in the centre. The expression of tenascin and a defined change in the expression of CK 17 indicates villous repair and hyperproliferative mechanisms in placental infarcts.

Antibody binding of high molecular cytokeratin proteins to villous and extravillous trophoblasts but not to human placental smooth muscle cells

Antibody binding of high molecular cytokeratin proteins to villous and extravillous trophoblasts but not to human placental smooth muscle cells

Apocrine nevus: light microscopic, immunohistochemical and ultrastructural studies of a case

The apocrine nevus (AN) is a rare tumor occurring in the upper chest and the axilla. We report a case of a AN in a 33-year-old female occurring unilaterally. The presenting complaint related to tenderness and swelling in the right axilla. The initial impression was hidradenitis suppurativa. The gross specimen revealed the presence of irregular thickening just beneath the dermal subcutaneous interface. Microscopically the lesion was composed of mature apocrine glands with apical snouts. The glands were arranged in lobules divided by thin fibrous septa. Immunohistochemical studies revealed the following profile in the glandular epithelium: positive low molecular weight cytokeratin, epithelial membrane antigen, and gross cystic disease fluid protein reactivity and negative high molecular cytokeratin and S-100 protein reactivity. Carcinoembryonic antigen reactivity was found in the duct epithelium. Ultrastructural studies revealed cells lining the lumen of the glands with a concentration of granules in the apical region and light and dark granules. These findings support the previously described light microscopic observations and provide unreported ultrastructural studies in this rare tumor.

Gastric small cell carcinoma with squamous and neuroendocrine differentiation

A rare gastric carcinoma containing diverse components, that is, neuroendocrine (small cell carcinoma), squamous and gland-like elements in an 82 yr old woman is described. Radiologic examination revealed a large ulcerated tumor, and a Borrmann type II tumor, 6.5 x 5 cm, was found in the resected stomach. Histologically, the tumor was mainly composed of small cells with hyperchromatic nuclei and scant cytoplasm. Argyrophilic granules were seen in these cells. There were also scattered foci of large cells with features of squamous cells, and many intermediate cells with oncocytic cytoplasm. The small cancer cells were positive for chromogranin A and neuron specific enolase. Squamous cell nests were positive for high molecular cytokeratin (CK), and intermediate cells were positive for low molecular CK. Electron microscopic examination revealed secretory granules in the small cells and tonofilaments in the squamous cells. This tumor might have originated from the pluripotential stem cell in the gastric epithelium.