Suhail Baithun

Expression of vascular endothelial growth factor (VEGF)-C and VEGF-D, and their receptor VEGFR-3, during different stages of cervical carcinogenesis.

Cervical carcinogenesis has well‐defined stages of disease progression including three grades of pre‐invasive lesions—cervical intraepithelial neoplasia grades 1–3 (CIN 1–3)—and invasive cervical cancer. However, the biological properties of CIN lesions prone to develop invasive disease are not well defined. Recent observations suggest that early invasive disease spreads to regional lymph nodes in several tumour types and that growth factors (VEGF‐C and VEGF‐D) involved in new lymphatic vessel formation may play a crucial role in this process. The present study has assessed the expression of VEGF‐C and VEGF‐D, and their receptor VEGFR‐3, in 152 cervical lesions (33 CIN 1, 33 CIN 2, 37 CIN 3, and 49 squamous cell carcinomas) to determine whether expression of lymphangiogenic factors occurs prior to invasion. The presence of lymphatic vessels was determined using LYVE‐1 and podoplanin staining, as well as double immunostaining for LYVE‐1/CD34 and podoplanin/CD34. In situ hybridization was performed to determine VEGFR‐3 mRNA expression. A significant positive correlation was found between VEGF‐C, VEGF‐D, and VEGFR‐3 expression through the different stages of cervical carcinogenesis. Significant differences in protein expression for VEGF‐C, VEGF‐D, and VEGFR‐3 were found between CIN 1–2 and CIN 3 (p < 0.001 for all), but not between CIN 3 and cervical cancer. More than 50% of the CIN 3 lesions showed moderate to strong staining for VEGF‐C and VEGF‐D, whereas most of the early pre‐cancerous lesions (CIN 1 and 2) were negative. In cervical cancer, similar observations to those in CIN 3 were found. VEGFR‐3 mRNA expression was found in the cytoplasm of epithelial neoplastic cells and VEGFR3 protein expression was found in more than 50% of CIN 3 lesions and cervical cancers, compared with 15% in CIN 1 and 2. These findings suggest an autocrine growth stimulation pattern via VEGFR‐3. Adjacent CIN 3 was present in nine cervical cancers and displayed strong expression for VEGF‐C, VEGF‐D, and VEGFR‐3. These results suggest that in cervical carcinogenesis a switch to the lymphangiogenic phenotype may occur at the stage of CIN 3. Copyright

Human papillomavirus-associated increase in p16INK4A expression in penile lichen sclerosus and squamous cell carcinoma

Background  Human papillomaviruses (HPVs) are sexually transmitted human carcinogens that may play a role in the oncogenesis of penile cancer.

Argyrophilic and hormone immunoreactive cells in normal and hyperplastic pancreatic ducts and exocrine pancreatic carcinoma

Scattered argyrophil cells were present in normal, large, medium-sized and small pancreatic ducts (ductules). There was marked increase in argyrophil cells in ducts with hyperplastic epithelium. Argyrophil cells were also found in 67.7% of all exocrine pancreatic carcinomas. In a well differentiated group including cystadenocarcinoma, mucinous carcinoma and well differentiated ductal adenocarcinoma argyrophil cells were found in all cases examined. Using four antisera (against insulin, glucagon, somatostatin and gastrin), insulin, glucagon and somatostatin cells were identified in 2.65%, 0.001% and 1.2% of normal ducts, and 7.5%, 2.4% and 4.6% of ducts with hyperplastic epithelium respectively and were also greatly increased in numbers in the latter group. Immunoreactive cells were present in 66.7% of exocrine carcinomas. Cells reactive for insulin were found in 7/15 cases; glucagon in 6/15 cases; somatostatin in 5/15 cases and gastrin in 2/15 cases. Eight cases contained two or more than two types of immunoreactive cells. The presence of argyrophil and hormone immunoreactive cells in pancreatic ducts and carcinomas is indicative of the close developmental relationship between endocrine and exocrine parts of the pancreas. The inter-relationship of response in the different cell types following stimulus suggests that injury to a common precursor may be involved.

Human papillomavirus is detected in transitional cell carcinoma arising in renal transplant recipients

Aims: We investigated the role of human papillomavirus (HPV) in the development of transitional cell carcinoma (TCC) arising in renal transplant recipients. Methods: Genomic DNA was extracted from 10 µm paraffin embedded sections of five TCCs arising in five renal transplant recipients using the QIAamp DNA mini kit according to the manufacturers instructions. β‐globin PCR was performed to test DNA adequacy. Samples were tested for the presence of HPV DNA by broad spectrum HPV PCR method using non‐biotinylated SPF10 primers (SPF1A, SPF1B, SPF1C, SPF1D, SPF2B, SPF2D) which amplify a short 65 bp fragment. Positive bands were identified on a 3% gel. Positive samples underwent a second HPV PCR and were amplified using biotinylated SPF10 primer set, which amplifies the same 65 bp region of the L1 open reading frame. INNO‐LiPA line probe assay was then performed to genotype the samples which uses a reverse hybridisation principle. Results: Four of five TCCs examined were positive for HPV. The high risk HPV16 was detected in three cases whereas in the fourth case an unclassifiable HPV genotype was present. In all DNA samples, β‐globin amplification was successful. Conclusions: Our results indicate that HPV and in particular HPV16 may play an aetiological role in the development of TCC in renal transplant patients.

Pathological effects of ionizing radiation

The effects of irradiation are commonly evident in a range of specimens dealt with by pathologists in routine clinical practice. Radiotherapy is frequently employed in the treatment of human malignancies and often patients will subsequently require surgery or, at least, tissue sampling to assess complications or recurrent tumour. Therefore, it is critical that all those involved in reporting of these specimens are aware of the range of effects that may occur in cells or tissues after irradiation. The most consistent changes seen after irradiation can be separated into early and late groups. The former result primarily from direct cellular toxicity with apoptosis and necrosis together with small vessel damage leading to endothelial cell injury, increased vascular permeability and stromal oedema. The chronic or delayed effects are dominated by degeneration and repair when morphological cellular abnormalities such as epithelial nuclear atypia and multinucleate stromal fibroblasts develop. At this later stage the vascular damage becomes more severe with intimal thickening, medial hyalinization, fibrinoid necrosis, luminal thrombosis and endarteritis obliterans. The vascular damage leads to ischaemic compromise with further stromal collagenous fibrosis and parenchymal atrophy. Rarely, malignant tumours may develop in the irradiated tissue after a latent period of several years. More detailed descriptions of specific tissue damage and mechanisms of radiation-induced injury are discussed.

Gonadotropins and Prostate Cancer – Revisited

Luteinizing hormone and follicle-stimulating hormone are called gonadotropins, because they stimulate the gonads – in males the testes and in females the ovaries. They are not necessary for life, but are essential for reproduction. In addition, the association of these hormones with prostate cancer has been the interest of many researchers. Their detection in the human prostate has been investigated using different methods, including immunologic and RT-PCR techniques. In addition, the increasing evidence of paracrine/autocrine functions of the gonadotropic glycoprotein hormones, their allocation to the superfamily of cystine knot growth factors, and luteinizing hormone/chorionic gonadotropin receptor gene expression in non-gonadal tissues led many researchers to investigate intraprostatic glycoprotein hormones and their receptor gene expression. We aim in this review to shed light on the physiology of the gonadotropins and their association with prostate cancer and highlight the future possibilities of their use as targets in treating this disease.

Asymptomatic Metastatic Adenocarcinoma of Glans Penis from Esophageal Cancer – A Rare Case Report and Review of Literature

Tumors metastasizing to the glans penis are uncommon and a rare occurrence. The majority of the primary tumors are located in the pelvis and they arise from the genitourinary tract and rectum (>75%). We report a 61-year-old man with known metastatic (lymph nodes and maxilla) esophageal cancer who was treated with chemotherapy and referred to urology with phimosis for circumcision. He did not have any other urological or penile complaints. During circumcision the glans penis looked nodular and a biopsy was taken. The histological examination of the biopsy showed metastasis from esophageal primary adenocarcinoma. The case was discussed in a multi-disciplinary meeting and palliative radiotherapy was recommended and commenced.