involucrin and Adenocarcinoma

Squamous differentiation/squamous metaplasia is often associated with endometrial adenocarcinoma and benign lesions, such as endometrial hyperplasia and chronic endometritis. Morules have distinct histological characteristics, and are referred to as squamous metaplasia or squamoid metaplasia.. To focus on the histological characteristics of morules and clarify the difference between morules and squamous differentiation.. Twenty endometrioid carcinomas with morules or squamous differentiation, five adenosquamous carcinomas, and eight non-carcinomatous endometrial lesions with morules were investigated. Numerous antibodies for epithelial membrane antigen (EMA), involucrin, cytokeratins, neuropeptides, and oncofetal antigens were used for immunohistochemistry. In situ hybridisation and polymerase chain reaction were used to detect human papillomavirus (HPV).. The morules observed were uniform cell clusters, with no squamous differentiation. They were immunonegative for epithelial antigens including involucrin, EMA, and cytokeratins, but were positive for neurone specific enolase. A few morules were immunopositive for acetylcholine esterase, and one case was positive for somatostatin; neither oncofetal nor proliferative cell markers, including blood group A, B, and AB, or other neuropeptides were demonstrated in the morules. HPV DNA was not found in either the morules in the carcinomas or in the benign lesions. However, true squamous differentiation tissue in four endometrioid carcinomas and two adenosquamous carcinomas was HPV positive using in situ hybridisation.. Morules are histologically distinct from squamous metaplasia/squamous differentiation tissue. Morules are thought to be neuroectodermal-like cell clusters, and are not infected with HPV. In contrast, some of the true squamous differentiation tissue was associated with HPV infection.

Topics: Adenocarcinoma; Adult; Aged; beta Catenin; Carcinoma, Squamous Cell; Cytoskeletal Proteins; DNA Mutational Analysis; DNA, Viral; Endometrial Neoplasms; Endometrium; Female; Humans; Immunohistochemistry; In Situ Hybridization; Metaplasia; Middle Aged; Papillomaviridae; Protein Precursors; RNA, Messenger; Trans-Activators; Transglutaminases

It has been reported previously in cases of adenosquamous carcinoma of the lung in Okinawa, a subtropical island 2000 km south of mainland Japan, that the squamous cell carcinoma components were positive for human papillomavirus (HPV) by non-isotopic in situ hybridisation (NISH). The adenocarcinoma cells adjacent to the squamous cell carcinoma components were enlarged and also positive for HPV. This is thought to indicate that after adenocarcinoma cells are infected with HPV, they undergo morphological changes, and that "squamous metaplasia" follows. In this present study, the effects of HPV transfection into adenocarcinoma cells were examined. The relation between the region expressing the HPV gene and squamous metaplasia was also studied.. Plasmid pBR322 containing HPV type 16 (HPV-16) was transfected into cultured colonic adenocarcinoma (DLD-1) and lung adenocarcinoma (PC-14) cells using the calcium phosphate method. Neomycin was used as a selection marker. The presence of HPV E1, E2, E4, E5, E6, E7, L1, and L2 mRNAs and also transglutaminase 1, involucrin, cyclin dependent kinases (CDKs), cyclins, caspases, apoptosis inducing factor, DNase gamma, Fas, and Fas ligand mRNAs in HPV transfected cells was investigated by means of reverse transcription polymerase chain reaction (RT-PCR). The G0-G1 cell population was analysed by flow cytometry. Morphological examination under light and electron microscopes was also carried out.. The virus transfected cells showed squamous metaplasia when they were injected into severe combined immunodeficient mice, expressing the high molecular weight keratin (Moll's number 1 keratin) and involucrin molecules immunohistochemically, and involucrin and transglutaminase I mRNAs by RT-PCR. The squamous metaplasia was most conspicuous in the HPV transfected DLD-1 cell when compared with HPV transfected PC-14 cells. Squamous metaplasia was most clearly demonstrated in one HPV transfected DLD-1 cell clone, which expressed not only E2 but also E6-E7 fusion gene mRNA. Viral L1 mRNA expression was absent in HPV transfected cell clones, and was not related to squamous metaplasia. The growth rate of HPV transfected cells was reduced. Transfection of the virus into the cultured adenocarcinoma cells increased the G0-G1 cell population greatly, as assessed by flow cytometer analysis. Furthermore, in the virus transfected cells, apoptosis was also observed by means of the terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labelling method.. HPV transfection into adenocarcinoma cells induced clear squamous metaplasia. One of the HPV transfected cell clones that expressed E2 and E6-E7 fusion gene mRNA showed the squamous metaplasia particularly clearly, and apoptosis was also demonstrated.

Topics: Adenocarcinoma; Animals; Apoptosis; Blotting, Western; Carcinoma, Squamous Cell; Cell Cycle; Cell Differentiation; DNA, Viral; Humans; Keratins; Lung Neoplasms; Metaplasia; Mice; Mice, SCID; Neoplasm Proteins; Neoplasm Transplantation; Papillomaviridae; Protein Precursors; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Viral; Transfection; Tumor Cells, Cultured

Non-small cell lung cancer (NSCLC) is fatal in approximately 90% of all cases due to the failure of systemic therapy, secondary to resistance to chemotherapy. In such malignancies new therapeutic paradigms are needed. One such approach takes advantage of normal physiologic growth regulatory mechanisms, such as terminal cellular differentiation or apoptosis. Suramin, as an antineoplastic drug, has shown efficacy in the treatment of prostate cancer and is capable of promoting differentiation in several human cancer cell lines. Little is known about the differentiating effects of suramin in lung cancer. In the present investigation we evaluated the ability of suramin to induce cross-linked envelope (CLE) formation, as a common marker for squamous differentiation and apoptosis, in three representative human non-small cell lung cancer cell lines: NCI-H226 (squamous), NCI-H358 (bronchoalveolar [adenocarcinoma]), and NCI-H596 (adenosquamous). Among agents that we have tested, suramin demonstrated the unique ability to induce spontaneous CLE formation in the two cell lines with squamous features, NCI-H226 and NCI-H596. Suramin induced CLE formation was accompanied by DNA fragmentation, a marker for apoptosis, in NCI-H596 and NCI-H358, but not in NCI-H226. Stimulation of CLE formation by suramin correlated with the rapid induction of both type II transglutaminase (TG) activity and involucrin expression. These parameters were protein synthesis independent, suggesting posttranslational mechanisms of suramin activity. Induction of differentiation/apoptosis markers by suramin did not correlate with its effect on growth. Modulation of signal transduction is a likely candidate mechanism for suramin activity in lung cancer. The relationship between growth, squamous differentiation, and apoptosis is considered.

Topics: Adenocarcinoma; Antineoplastic Agents; Apoptosis; Calcimycin; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Cell Differentiation; Cell Division; DNA Fragmentation; Enzyme Inhibitors; Humans; Ionophores; Lung Neoplasms; Neoplasm Proteins; Protein Kinase C; Protein Precursors; Putrescine; Suramin; Transglutaminases; Tumor Cells, Cultured

Adenosquamous carcinoma and squamous cell carcinoma (SCC) occur rarely in the liver compared with adenocarcinoma, and the histogenesis and biologic behaviors of these tumors remain unknown. The authors addressed these issues in the current article.. A specimen aseptically obtained from the surgically resected cholangiocellular carcinoma (CCC) was cut into pieces and inoculated into the back of a nude mouse, bilaterally. The developed tumors were resected and serially transplanted into nude mice. The morphologic features and growth kinetics of the nude mouse tumors at different passages were compared.. The authors established a new human CCC nude mouse strain, designated nuKMC-2, from a 64-year-old woman. The original tumor of the patient showed the features of moderately differentiated tubular adenocarcinoma with small sheet-like arrangement of polygonal cells. The initial tumor developed in a nude mouse showed morphologic features similar to the original tumor. With the serial transplantation to nude mice, the components of tubular adenocarcinoma diminished, and all of the nuKMC-2 was replaced by SCC. Doubling times of nuKMC-2 at the 5th and 11th passages were 9.9 and 7.4 days, respectively, which suggested that the tumor with squamous components were more aggressive biologically than the adenocarcinoma.. The results suggested that adenosquamous carcinoma might be a transitional form from adenocarcinoma to SCC and that some of the primary hepatic SCC might originate from adenocarcinomas.

Topics: Adenocarcinoma; Adenoma, Bile Duct; Animals; Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Bile Duct Neoplasms; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Mice; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Neoplasm Transplantation; Protein Precursors; Serpins

Using immunoperoxidase stain for involucrin, 50 well-differentiated adenocarcinomas of the lung were compared with similarly well-differentiated adenocarcinomas of other organs, 30 from the stomach, 30 from the colon, 12 from the pancreas and 12 from the prostate. Thirty (60%) adenocarcinomas of the lung were positive for involucrin; in 24 of 30 cases from 10% to more than 60% of tumor cells were positive and in the remaining 6 cases a few cells were positive. The positive cells included columnar or cuboidal tumor cells as well as some squamoid tumor cells. In contrast, only 4 (4.8%) of 84 tumors in the other organs were involucrin positive. Most of the involucrin positive foci of these four cases seemed to show squamous differentiation. These findings suggest that pulmonary adenocarcinoma is more prone to show squamous differentiation, compared with gastric, colonic, pancreatic and prostatic adenocarcinomas. The result may be applied for the differential diagnosis between primary and metastatic well-differentiated adenocarcinomas in the lung.

Topics: Adenocarcinoma; Cell Differentiation; Colonic Neoplasms; Humans; Immunoenzyme Techniques; Lung Neoplasms; Male; Pancreatic Neoplasms; Prostatic Neoplasms; Protein Precursors; Stomach Neoplasms

Forty nasopharyngeal carcinomas (NPC) were studied by immunohistochemistry using an antibody to involucrin and the following three keratin antibodies: (1) an antibody to low molecular weight keratin reactive with nonsquamous epithelium, (2) a high molecular weight keratin antibody reactive with suprabasal squamous epithelium, and (3) a keratin antibody reactive with full thickness stratified epithelium. In its pattern of reactivity, the last antibody overlaps the low and high molecular weight keratin antibodies and is used as a broad spectrum keratin antibody. By World Health Organization (WHO) classification, the cases in this article included eight keratinizing squamous cell carcinomas, eight nonkeratinizing carcinomas, 20 undifferentiated carcinomas, and four adenocarcinomas. The antibody to broad spectrum keratin had an overall sensitivity of 87.5% and was positive in all eight keratinizing squamous cell carcinomas, seven nonkeratinizing carcinomas (87.5%), 18 undifferentiated carcinomas (90%), and two adenocarcinomas (50%). Low molecular weight keratin antibody stained one additional NPC, which was negative when broad spectrum keratin antibody was used. Involucrin and high molecular weight keratin antibodies demonstrated near parallel staining in all histologic classes; there was marked localization to areas of squamous differentiation. While involucrin is a marker for foci of greater squamous differentiation, broad spectrum keratin antibody may aid in the diagnosis of all histologic subtypes of NPC.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Antibody Specificity; Carcinoma; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Protein Precursors

A study was undertaken to determine whether immunoperoxidase stains for keratin and involucrin, the latter a protein present in cells of stratified squamous epithelium that have differentiated beyond the basal stage, distinguish any differences in squamous cells present in the adenoacanthoma from those in the adenosquamous carcinoma of the uterine corpus. Forty-eight tumors were studied, of which 33 were adenoacanthomas and 15 adenosquamous carcinomas. The patients with adenoacanthomas were slightly younger (mean 61.5 vs. 64.5 years) and had tumors that were generally better differentiated than the adenosquamous carcinomas. The squamous epithelium in every tumor, regardless of histologic type, stained positively for keratin. There were no obvious differences in staining when tumors were stratified for histologic type, grade, or location within the tumor. The glandular portion of both tumor types stained irregularly, but nonetheless positively, for keratin in 71% of the cases. Involucrin was detected in 57% of adenoacanthomas and 87% of adenosquamous carcinomas. The deeper or more central portion of the squamous morules stained only if the more superficial or peripheral areas were positive. The extent of the involucrin staining was less in the adenosquamous carcinomas than in the adenoacanthomas. The glandular component of the tumors did not stain for involucrin. It is concluded that no qualitative differences in the staining reactions with respect to keratin and involucrin distinguish the adenoacanthomas from the adenoaquamous carcinoma. These findings support the argument that the adenoacanthoma and adenosquamous carcinoma represent a spectrum of squamous differentiation in a single tumor type.

Topics: Adenocarcinoma; Adult; Aged; Carcinoma, Squamous Cell; Cell Differentiation; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Keratins; Middle Aged; Protein Precursors; Uterine Neoplasms

Involucrin is a precursor of the cross-linked envelope protein or marginal band present in human stratum corneum. This study uses immunohistochemical techniques for localization of involucrin in histologic sections from 91 lung tumors in order to evaluate the usefulness of involucrin as a tumor marker in lung neoplasms. Although involucrin is absent from bronchial epithelium, it is expressed in cultured tracheal epithelial cell colonies and in bronchial mucosa with squamous metaplasia. Involucrin was present in all 25 cases of squamous and adenosquamous carcinoma. Staining was focal in 12 cases of squamous cell carcinoma and was most marked in the larger neoplastic cells in the center of squamous cell nests. Only two of 20 cases of adenocarcinoma revealed focal staining for involucrin, and these cases may represent adenosquamous variants. Six of 12 cases of large cell undifferentiated carcinoma stained for involucrin, indicating squamous differentiation, and seven cases of malignant mesothelioma were negative. Isolated involucrin-positive cells were present in two of 16 cases of small cell anaplastic carcinoma and one of 11 carcinoid tumors, identifying variants of neuroendocrine tumors with dual differentiation. Patterns of localization of involucrin in paraffin and frozen sections were compared with staining for cytokeratins in parallel sections. Immunohistochemical localization of involucrin comprises a specific marker for squamous differentiation in lung tumors.

Topics: Adenocarcinoma; Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Humans; Lung Neoplasms; Mesothelioma; Protein Precursors; Staining and Labeling