Background: Despite advances in diagnostic and treatment strategies, head and neck squamous cell cancer (HNSCC) constitutes one of the worst cancer types in terms of prognosis. PTEN is one of the tumour suppressors whose expression and/or activity have been found to be reduced in HNSCC, with rather low rates of mutations within the PTEN gene (6-8%). We reasoned that low expression levels of PTEN might be due to a transcriptional repression governed by an oncogene. Tbx2 and Tbx3, both of which are transcriptional repressors, have been found to be amplified or over-expressed in various cancer types. Thus, we hypothesize that Tbx3 may be over expressed in HNSCC and may repress PTEN, thus leading to cancer formation and/or progression. Methods: Using immunohistochemistry and quantitative PCR (qPCR), protein and mRNA levels of PTEN and Tbx3 were identified in samples excised from cancerous and adjacent normal tissues from 33 patients who were diagnosed with HNSCC. In addition, HeLa and HEK cell lines were transfected with a Tbx3 expressing plasmid and endogenous PTEN mRNA and protein levels were determined via qPCR and flow cytometry. Transcription assays were performed to demonstrate effects of Tbx3 on PTEN promoter activity. Mann–Whitney, Spearman’s Correlation and Wilcoxon signed-rank tests were used to analyze the data. Results: We demonstrate that in HNSCC samples, Tbx3 mRNA levels are increased with respect to their normal tissue counterparts (p<0.001), whereas PTEN mRNA levels are significantly reduced in cancer tissues. Moreover, Tbx3 protein is also increased in HNSCC tissue sections. Over-expression of Tbx3 in HeLa and HEK cell lines causes reduction in endogenous PTEN mRNA and protein levels. In addition, transcription activity assays reveal that Tbx3 is capable of repressing both the basal and induced promoter activity of PTEN. Conclusions: We show that Tbx3 is up-regulated in tissue samples of HNSCC patients and that Tbx3 represses PTEN transcription. Thus, our data not only reveals a new mechanism that may be important in cancer formation, but also suggests that Tbx3 can be used as a potential biomarker in cancer.

Ectopic breast tissue can occur anywhere along the primitive embryonic milk line and can be the site of the same pathologic processes found in the normal breast. Phyllodes tumor is an extremely rare fibroepithelial neoplasm that occurs in ectopic breast tissue of the vulva. To date, only 8 cases of phyllodes tumor in the vulva have been reported in the literature. This paper presents two additional case of benign phyllodes tumor in the vulva. The first patient was a 43-year-old woman, presenting with a lesion on the left anterior mons pubis that had increased in size in the last three months. The second patient was a 50-year-old woman, presenting with a two-month history of a mass in the right labium majus. The patients underwent excisional biopsy. The histological examination of both specimens revealed a characteristic pattern of benign phyllodes tumor. In conclusion, the pathologists need to be aware that the lesion can occur in this location. Herein, the concepts about the histogenesis of phyllodes tumor in the vulva are discussed and a brief review of the previously reported cases is given.

Pulmonary alveolar microlithiasis is characterized by the presence of calcospherites in alveolar spaces. Sporadic cases are more common, but the disease also presents in an inherited familial form. The greatest number of reported cases is from Europe and especially Turkey. We present a 43-year-old female with complaints of dyspnea for many years. She had a suspicious familial history of pulmonary alveolar microlithiasis. The surgical lung biopsy specimen appeared gritty and firm. Histological sections showed diffuse involvement of the lung parenchyma by innumerable tiny calcospherites. Genetic studies showed a homozygous c.316G > C (p.G106R) mutation in exon 4 and confirmed the diagnosis of pulmonary alveolar microlithiasis. The present report aims to contribute to the literature with a pathologically and genetically confirmed new case to add insight into the etiology of this rare disease. This case confirms an autosomal recessive inheritance and does not support the role of non-genetic and other factors in the pathogenesis of pulmonary alveolar microlithiasis.