PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients.

BACKGROUND: Agents targeting programmed death-1 receptor (PD-1) and its ligand (PD-L1) are showing promising results in non-small-cell lung cancer (NSCLC). It is unknown whether PD-1/PD-L1 are differently expressed in oncogene-addicted NSCLC. METHODS: We analysed a cohort of 125 NSCLC patients, including 56 EGFR mutated, 29 KRAS mutated, 10 ALK translocated and 30 EGFR/KRAS/ALK wild type. PD-L1 and PD-1 expression were assessed by immunohistochemistry. All cases with moderate or strong staining (2+/3+) in >5% of tumour cells were considered as positive. RESULTS: PD-1 positive (+) was significantly associated with current smoking status (P=0.02) and with the presence of KRAS mutations (P=0.006), whereas PD-L1+ was significantly associated to adenocarcinoma histology (P=0.005) and with presence of EGFR mutations (P=0.001). In patients treated with EGFR tyrosine kinase inhibitors (N=95), sensitivity to gefitinib or erlotinib was higher in PD-L1+ vs PD-L1 negative in terms of the response rate (RR: P=0.01) time to progression (TTP: P<0.0001) and survival (OS: P=0.09), with no difference in PD1+ vs PD-1 negative. In the subset of 54 EGFR mutated patients, TTP was significantly longer in PD-L1+ than in PD-L1 negative (P=0.01). CONCLUSIONS: PD-1 and PD-L1 are differentially expressed in oncogene-addicted NSCLC supporting further investigation of specific checkpoint inhibitors in combination with targeted therapies.

Dirofilariasis due to Dirofilaria repens in Italy, an emergent zoonosis: report of 60 new cases.

AIMS: Sixty new cases of human dirofilariasis due to Dirofilaria repens, occurring in Italy between 1990 and 1999, are presented. This is the most extensive case study of this zoonosis reported worldwide by a single study group. The aim is to utilize this large experience to characterize the different histopathological findings in the parasitic lesions in man. METHODS AND RESULTS: Diagnosis was performed on histological sections of the nematode enclosed in the nodules excised at biopsy or surgery. The nematode was located in the subcutaneous tissue (49 cases), the epididymis (two cases), the spermatic cord (two cases), the lung (two cases), the breast (two cases), the omentum (two cases) and under the conjunctival tissue (one case). The majority of cases (46) were from Piedmont; the remainder were from Emilia-Romagna, Sardinia, Sicily, Tuscany, Apulia and Lombardy. The histopathological features of the lesions are described and the clinical and epidemiological aspects of the zoonosis are discussed. The prevalence in Italy in general and in the area of Piedmont in particular, comprising the provinces of Alessandria, Asti, Novara and Vercelli, which is one of the most severely affected areas of the world, is emphasized. The evident increase in the number of cases in the last few years is a clear indication that it is an emergent zoonosis. CONCLUSIONS: We recommend that each and every case observed be recorded, to enable the true extent of human dirofilariasis in Italy to be assessed, and that a reference centre be set up in the area to collate the data. The importance of the histopathologist's role in the diagnosis is stressed.

Relationship between progesterone receptor, axillary node status and productive fibrosis in ductal infiltrating carcinoma of the breast.

The presence of progesterone receptor (PR), productive fibrosis (PF), axillary nodal status and tumor size are important prognostic variables in breast cancer. In this study we have analyzed the relationship between these four parameters in 78 ductal infiltrating carcinomas of the breast. No relationship was found between PF and the presence of lymph node metastatic disease: however, in the tumors with positive nodes, a limited metastatic diffusion (1-3 lymph nodes) was significantly associated with PF (p less than 0.05). Our study failed to demonstrate any relation between estrogen receptor (ER) and both presence and extension of nodal involvement; in contrast, the tumors with limited metastatic diffusion (1-3 lymph nodes) had a significantly higher prevalence of PR positivity (p less than 0.05). Furthermore, PF was strongly associated with PR (p less than 0.001) and less well with ER (p less than 0.05). The simultaneous presence of PR and marked PF was strongly correlated with limited metastatic involvement of the axilla (p less than 0.007). Tumor size was correlated with the number of positive nodes (p less than 0.001), but not with PR or PF. The results demonstrate that PR status, PF and tumor size are related to limited metastatic diffusion of the axilla: furthermore PF and PR have been shown to be strongly related and we have demonstrated that, at least in ductal infiltrating carcinoma, the simultaneous presence of them identifies a subset of tumors with low metastatic capacity independently of tumor size.