Mesonephric Adenocarcinoma of the Vagina Harboring TP53 Mutation

Mesonephric adenocarcinoma (MA) of the female genital tract is a rare but distinct entity, exhibiting unique morphological, immunophenotypical, and molecular characteristics. Vaginal MA is hypothesized to arise from the mesonephric remnants located in the lateral vaginal wall. A 52-year-old woman presented with vaginal bleeding. Physical examination revealed a protruding mass in the left vaginal wall. Pelvic magnetic resonance imaging revealed a 2.5-cm mass arising from the left upper vagina and extending posterolaterally to the extravaginal tissue. The punch biopsy was diagnosed as poorly differentiated adenocarcinoma. She received radical surgical resection. Histologically, the tumor displayed various architectural patterns, including compactly aggregated small tubules, solid cellular sheets, endometrioid-like glands and ducts, intraluminal micropapillae, cribriform structure, and small angulated glands accompanied by prominent desmoplastic stroma. The tubules and ducts possessed hyaline-like, densely eosinophilic intraluminal secretions. The tumor extended to the subvaginal soft tissue and had substantial perineural invasion. Immunostaining revealed positivity for the mesonephric markers, including GATA3, TTF1, and PAX2, while showing very focal and weak positivity for estrogen receptor and negativity for progesterone receptor. Additionally, we observed a complete absence of p53 immunoreactivity. Targeted sequencing analysis revealed that the tumor harbored both activating KRAS p.G12D mutation and truncating TP53 p.E286* mutation. A thorough review of the previous literature revealed that 4.5% (3/67) of vaginal/cervical MAs and 0.9% (1/112) of uterine/ovarian mesonephric-like adenocarcinomas harbor TP53 mutations, indicating that this is very uncommon in malignant mesonephric lesions. In summary, we presented a rare case of vaginal MA uniquely harboring pathogenic TP53 mutation, resulting in p53 aberration.

Involvement of Felis catus papillomavirus type 2 in the tumorigenesis of feline Merkel cell carcinoma

Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine tumor. We recently demonstrated that cats with MCC often have other proliferative cutaneous lesions, such as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Based on this finding, we hypothesize that Felis catus papillomavirus (FcaPV) is involved in the development of MCC in cats, similar to SCC and BCC. To investigate this hypothesis, the presence of FcaPV nucleic acid and immunoreactivity for tumor suppressor proteins were examined in 21 feline MCC cases. Polymerase chain reaction using FcaPV type-specific primers detected FcaPV2 DNA in 20/21 samples of MCC. The complete FcaPV2 sequence was characterized in one case. In situ hybridization for FcaPV2 E7 revealed punctate nuclear signals within tumor cells in 19/21 MCC. Increased immunoreactivity for p16CDKN2A protein and decreased immunoreactivity for retinoblastoma (pRb) and p53 proteins were observed in 20/21 MCC. These results suggest that feline MCC cases are infected with FcaPV2 and the subsequent inhibition of pRb and p53 induced by integrated viral oncogenes is associated with feline MCC tumorigenesis, similar to other PV-induced proliferative cutaneous lesions. On the other hand, the single case of FcaPV2-negative MCC showed strong p53 immunoreactivity, suggesting mutations in p53 caused by cancer inducers other than FcaPV2 infection in this case. The present study suggests FcaPV2 as a cause of feline MCC.

Age-dependent changes of p53 and p63 immunoreactivities in the mouse hippocampus

P53 and its family member p63 play important roles in cellular senescence and organismal aging. In this study, p53 and p63 immunoreactivity were examined in the hippocampus of young, adult and aged mice by using immunohistochemistry. In addition, neuronal distribution and degeneration was examined by NeuN immunohistochemistry and fluoro-Jade B fluorescence staining. Strong p53 immunoreactivity was mainly expressed in pyramidal and granule cells of the hippocampus in young mice. p53 immunoreactivity in the pyramidal and granule cells was significantly reduced in the adult mice. In the aged mice, p53 immunoreactivity in the pyramidal and granule cells was more significantly decreased. p63 immunoreactivity was strong in the pyramidal and granule cells in the young mice. p63 immunoreactivity in these cells was apparently and gradually decreased with age, showing that p63 immunoreactivity in the aged granule cells was hardly shown. However, numbers of pyramidal neurons and granule cells were not significantly decreased in the aged mice with normal aging. Taken together, this study indicates that there are no degenerative neurons in the hippocampus during normal aging, showing that p53 and p63 immunoreactivity in hippocampal neurons was progressively reduced during normal aging, which might be closely related to the normal aging processes.

Immunohistochemical expression of P53 in basal cell carcinoma of skin.

Objectives: To evaluate the immunohistochemical expression of p53 in basal cell carcinoma of skin. Study Design: It was cross sectional study. Setting: Pathology department of Pakistan Institute of Medical Sciences Hospital, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan. Period: Six months after approval from the Hospital Ethical Committee. Material and Methods: In a descriptive background, 50 cases were involved in the study. Cases were selected by non-probability consecutive sampling technique. Patients of all age group (Males and Females) that was diagnosed as basal cell carcinoma of skin by Hematoxylin & Eosin were included in study. Other epithelial tumors of skin, appendageal tumors and metastatic tumors were excluded. Cases were evaluated for expression of tumor suppressor protein-p53 by immunohistochemical technique applied on formalin-fixed paraffin-embedded blocks. Results: Out of 50 cases, majority of patients were found to be male. Ratio of male to female was 2.6:1. Age range of patient was found between 21-98 years. Mainstream of the patients were between 41-60 years. Nose was found to be frequently involved site 28 (56%) cases. p53 expression was seen in 42 (84%) cases while in 8 (16%) cases p53 expression was not seen. Conclusion: It was found that p53 expression rate is very high in basal cell carcinoma of skin. This high expression of p53 immunoreactivity was explained in terms of its pathogenetic role and mutation in basal cell carcinoma.

HPV-related Vulvar Diseases and Perspectives of p16INK4a Immunochemistry: A Review of the Literature

Introduction Two different types of vulvar intraepithelial neoplasia (VIN), HPV-related and HPV-unrelated, should be considered as two separate entities with different management options. The incidence of HPV-related VIN is increasing worldwide and is implicated in carcinogenesis. Our objective is to investigate the use of p16INK4a immunostaining or p16INK4a/p53 double staining for the detection of HPV-related disease to overcome the problem that histological criteria often have significant overlap. Methods A systematic literature search was carried out in the online databases PubMed, EMBASE, Cochrane Library, Clincaltrials.gov and Scopus. The key search terms were HPV, VIN, p16INK4a immunochemistry and p53. Results We found that nuclear and cytoplasmic immunostaining for p16INK4a was intense and diffuse in HPV-associated lesions and weak and focal in normal vulvar epithelium, nondysplastic lesions, lichen sclerosus and keratinizing vulvar squamous cell carcinoma. p53 nuclear immunostaining was always negative in HPV-related disease. Conclusions Our findings indicated that p16INK4a or p16INK4a/p53 immunoreactivity, along with histological diagnosis, could be a convenient means to adequately classify VIN and its connection to HPV infection. Therefore, the clear recognition of HPV-associated VIN would lead to an appropriate strategy of treatment and follow-up.

Eradication of Helicobacter pylori Infection Restores ki67, p53, and Cyclin D1 Immunoreactivity in the Human Gastric Epithelium

Introduction We evaluated the effect of Helicobacter pylori (HP) eradication on p53, cyclin D1 expression, and cell proliferation in gastric mucosa. Materials and Methods We assessed p53, cyclin D1, and ki67 immunoexpression in gastric mucosa from 31 HP chronic gastritis patients and 12 controls. Reassessment was performed 6 months after successful HP eradication. Results Successful eradication resulted in significant decrease of p53 (1.53 ± 0.16 vs 0.83 ± 0.19, P = 0.01) and ki67 (9.84 ± 0.96 vs 4.77 ± 0.27, P < 0.001) staining in the antrum. Similarly, p53 immunoreactivity significantly decreased in the corpus (1.27 ± 0.20 vs 0.46 ± 0.15, P = 0.02), while there was a trend for decreased corpus cyclin D1 and ki67 expression (0.17 ± 0.07 vs 0.0, P = 0.08 and 8.71 ± 1.24 vs 5.85 ± 0.54, P = 0.09, respectively). Importantly, after successful HP eradication, the immunoreactivity of the studied parameters was similar to that of controls. Conclusion Successful HP infection eradication restores p53, cyclin D1, and ki67 immunoreactivity in the gastric mucosa to the level of controls.

Correlation of p53 immunoexpression with DNA ploidy and apoptotic index in subsets of prostate cancer: A marker reiterated in progression and recurrence of prostate cancer

Background: Prediction of biological behavior in patients of prostate cancer (CaP) is a major challenge as current parameters only partially meet the need for prognostication. p53 as a prognostic indicator has been studied in several human cancers, including breast, lung, and colorectal carcinoma. However, its significance as a predictive biomarker for CaP is less well-studied. Materials and Methods: This study included 125 cases of CaP, 27 cases of prostatic intraepithelial neoplasia and 25 cases of benign prostatic hyperplasia. Immunohistochemical assessment for p53 nuclear protein was performed. Assessment for apoptotic index and DNA ploidy status by flow cytometry were also done. Results: p53 immunoreactivity was low in organ confined CaP cases having Gleason score ≤3 (P < 0.003). More hormone resistant cases 37 (83%) were aneuploid when compared with hormone sensitive cases 26 (33%) (P < 0.005). 93% of p53 positive cases and none of the p53 negative patient were aneuploid suggesting a significant relation between p53 immunoreactivity and aneuploidy. p53 positivity and DNA aneuploidy, independently, were also predictors of progression and relapse. Conclusion: DNA ploidy and p53 positivity go hand in hand and together yield additional prognostic information in CaP. p53 positivity is possibly a late event in carcinogenesis in CaP and a marker of change in biological behavior of CaP.