Evaluation of HER2 and p53 expression in predicting response to docetaxel-based first-line chemotherapy in advanced breast cancer

Background

The human epidermal growth factor receptor 2 (HER2) and p53 pathways may be involved in chemotherapy sensitivity and/or resistance. We explore the value of HER2 and p53 status to foretell docetaxel sensitivity in advanced breast cancer.

Methods

HER2 and p53 expression was analysed in 36 (median age 55 yrs; range 37-87) metastatic breast cancer patients receiving docetaxel-based first-line chemotherapy. HER2 was determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), p53 was tested by IHC. We correlate the expression of study parameters with pathologic parameters, RECIST response and survival. The standard cut-off value of 2 was used to determine HER2 overexpression while p53 mean expression level was used to divide low/high expressors tumors.

Results

Median time to progression and overall survival were 9 (range 2 - 54) and 20 (range 3 - 101) months. Overall response rate was 41.6%. Nine cases showed HER2 overexpression. HER2 was more frequently overexpressed in less differentiated (p = 0.05) and higher stage (p = 0.003) disease. Mean FISH-HER2 values were significantly higher in responder than in non-responder pts (8.53 ± 10.21 vs 2.50 ± 4.12, p = 0.027). Moreover, HER2 overexpression correlates with treatment response at cross-tabulation analysis (p = 0.046). p53 expression was only associated with higher stage disease (p = 0.02) but lack of any significant association with HER status or docetaxel response. No significant relation with survival was observed for any parameter.

Conclusion

Our data seem to indicate that FISH-determined HER2 status but not p53 is associated with docetaxel sensitivity in metastatic breast cancer.     

Human papillomavirus therapeutic vaccines in head and neck tumors

Head and neck cancer represents one of the most challenging diseases as the mortality remains high despite advances in early diagnosis and treatment. Human papillomavirus has been implicated in a third of head and neck squamous cell carcinomas and human papillomavirus type 16 is strongly associated with carcinomas arising from the oropharynx, the tonsil being the preferred infected site. Novel therapeutic approaches including immunotherapy are currently under investigation. Immune vaccines developed against human papillomavirus in the genital area are already available and could simultaneously protect other anatomical localizations; however, prophylactic vaccines are expected to be effective in reducing the incidence of tumors after many years and, therefore, there is an urgent need to improve therapeutic interventions, such as immunotherapy. To date, human papillomavirus therapeutic vaccines are either at the preclinical level or at early phase human trials for genital pathologies. Nevertheless, accumulating evidence from animal and clinical studies suggests that the enhancement of specific and innate immune responses is effective in clearance of the human papillomavirus infection, promoting a cautious optimism regarding the achievement of an efficacious immunotherapy. This article reviews what has been achieved and what remains to be done in the field for the development of future viral vaccines in head and neck tumors.     

Treatment response profiles: An extension of the double dissociation concept in neuropsychological research

The presence of double dissociations in patients with neurological damage has long been used as evidence that the dissociated functions cannot be explained in terms of a common system or module. Shallice (1988) has suggested that a second procedure, the double critical variable method, can provide evidence for a similar conclusion. In this paper we examine the situation where double dissocations are not naturally present, suggesting that the two phenomena are merely aspects of the same underlying condition. We propose that the logic of the double critical variable method can be applied in this situation, whenever responses to treatment vary in a particular manner across syndromes and patients. This logic was previously used by Beschin, Cocchini, Allen, and Della Sala (2012) to show a dissociation between anosognosia and neglect in stroke patients; we suggest that it might have a more general application. As an aid in understanding the concept we also introduce the performance/performance curve; this builds on the existing idea of performance/resource curves to draw a single graph from two such curves, whose points may be derived from direct observation. It enables the empirical testing of hypotheses about the functional form of unobservable performance/resource relationships, and may be of use beyond the existing application to treatment response profiles.     

Overexpression of p53 and bcl-2 proteins and the presence of HPV infection are independent events in head and neck cancer

The expression of p53 and bcl-2 proteins by immunohistochemistry and the identification of human papillomavirus (HPV) infection by a non-isotopic polymerase chain reaction (PCR)based method were investigated in 30 patients with head and neck cancer. Ten cases were HPV-positive (33%), mostly as double or multiple infections by high- or intermediate-risk types. Twenty-one patients were p53-positive (70%), 9/10 with HPV-positive tumours and 12/20 with HPV-negative tumours; this difference was not statistically significant. Only four cases were bcl-2-positive, irrespective of the presence of either HPV or p53. No correlation was found between these biological factors and tumour stage, differentiation grade, and alcohol or tobacco use. Our findings indicate that p53 is involved in the majority of cases, bcl-2 is rare, and high-risk HPV could play a key role, especially in tumours of tongue and tonsil. In conclusion p53 and bcl-2 protein expression and the presence of HPV infection are independent events in these malignancies.     

A case of ureteral lesions in a renal transplant recipient with a co-infection of BK virus and JC virus

Sir, Most cases of Polyomavirus-associated nephropathy are due toBKV, although Randhawa [1] demonstrated the co-infection ofJCV and BKV in renal transplant recipients with interstitialnephritis and Kazory [2] and Wen [3] described two cases ofinterstitial nephritis associated     

Case reports: zoster pain in haematological malignancies: effective pain relief with oxycodone in patients unresponsive to other analgesic measures

Varicella zoster virus (VZV) outbreak is a significant cause of morbidity in patients suffering from blood-related malignancies, occurring mostly among those affected by lymphoproliferative disorders and in those receiving haematopoietic stem-cell transplantation. The elucidated pathological mechanisms of VZV-related painful complications have provided the rationale for acute zoster pain (AZP) and post-herpetic neuralgia (PHN) treatment with antiviral therapy combined with neuroactive agents, such as tricyclic or anticonvulsant agents. The role of opioids in this setting is less clearly established. We successfully treated (with oxycodone) 12 consecutive patients suffering from AZP and long-lasting PHN resistant to several agents, including anticonvulsants and analgesics. Our experience is reported together with a brief overview of the management of these often distressing and intractable complications.