M. Ruhul Quddus

The effect of neoadjuvant chemotherapy on estrogen and progesterone receptor expression and hormone receptor status in breast cancer

BACKGROUND Neoadjuvant chemotherapy may decrease tumor volume to allow breast conservation surgery. Its effect on estrogen and progesterone receptor (ER/PR) expression and hormone receptor (HR) status is controversial. METHODS From February 2001 to July 2002, 56 breast cancer patients treated with neoadjuvant chemotherapy and 56 non-neoadjuvant therapy (control) patients with adequate tissue samples were identified. Quantitative ER/PR expression was analyzed in preneoadjuvant or preoperative core biopsies and final surgical specimens. Changes between the two groups were compared to determine if alterations were due to neoadjuvant chemotherapy or tissue sampling. RESULTS The ER/PR expression changed in 34 (61%) neoadjuvant chemotherapy patients and 27 (48%) control patients. These expression changes resulted in HR status (positive/negative) alterations in 3 patients (5%) in both groups. Age, histology, chemotherapy regimen, and neoadjuvant response did not predict change. CONCLUSIONS Hormone receptor status changed in 5% of neoadjuvant chemotherapy and control groups due to tissue sampling. As these changes may impact treatment, HR expression reanalysis in final surgical specimens is recommended.

Minor serous and clear cell components adversely affect prognosis in ''mixed-type'' endometrial carcinomas: a clinicopathologic study of 36 stage-I cases.

Most endometrial carcinomas contain only 1 Müllerian cell type although the presence of 2 or more cell types within 1 tumor, for example a predominantly low-grade endometrioid carcinoma with a minor component (arbitrarily defined as 30% or less) of high-grade serous and/or clear cell carcinoma, is not uncommon. The current study attempts to evaluate whether the presence of minor serous or clear cell components exerts an adverse effect on the prognosis in stage-I endometrial carcinomas of ‘‘mixed-type.’’ The study cases include 22 cases of stage-I endometrioid carcinoma with a minor component of serous carcinoma and 14 cases of endometrioid carcinoma with a minor component of clear cell carcinoma. Minor components were arbitrarily defined as representing anywhere between 5% and 30% of the total tumor. The study cases were compared with 56 cases of histologically pure age-matched and stage-matched endometrioid carcinomas, 6 pure serous carcinomas, and 13 pure clear cell carcinomas. All study and control cases were fully staged. Treatment history and outcome status were obtained and follow-up ranged from 56 to 140 months. Our study suggests that the presence of minor components of serous and clear cell carcinoma, defined as between 5% and 30%, within a mixed-type endometrial carcinoma appears to adversely influence the long-term survival of stage-I tumors, although a larger study is needed to corroborate our findings.

Simplex (differentiated) type VIN: absence of p16INK4 supports its weak association with HPV and its probable precursor role in non-HPV related vulvar squamous cancers

any histological resemblance to tumours of Müllerian origin support such a diagnosis. The most effective therapy is complete surgical excision, while the role of adjuvant radiotherapy and chemotherapy remains controversial. The FATWO should be distinguished from granulosa cell tumours, mainly of the diffuse or the infantile type, Sertoli-Leydig cell tumours and adenomatoid tumours and endometrioid carcinomas of the Fallopian tubes. The resemblance to these tumours, however, is only superficial and, if sufficient tissue is examined, the Wolffian origin of the tumour becomes apparent. Endometrioid carcinoma of the Fallopian tube usually occurs as an intralumenal mass and has abnormal hyperchromatic nuclei and high mitotic activity. Intralumenal mucin is common, and reticulin is arranged around groups of neoplastic glands that are EMA-positive. Sertoli-Leydig cell tumours more commonly occur in young females, aged 20–30 years, and develop in the ovaries, rather than the broad ligaments or the mesosalpinx. More importantly, they contain typical Leydig cells with abundant eosinophilic granular cytoplasm, and may be associated with endocrine manifestations due to androgen secretion. In addition, Sertoli-Leydig cell tumours often express a-inhibin. Granulosa cell tumours are composed of typical cells exhibiting longitudinal nuclear grooving and a strong diffuse inhibin positivity. Adenomatoid tumours also contain cyst-like spaces, but these are set in a connective tissue stroma that is often hyalinized and contains smooth muscle fibres. Nonetheless, it has been reported that among 25 FATWO seen in consultation, the correct diagnosis was considered by the referring pathologist in only 17%. The biological behaviour of these tumours is unpredictable but is, in general, benign. This is only the seventh malignant tumour described thus far, with distinctive morphological features being the large size of the tumour, larger than 100 mm, apparent hypercellularity, capsular invasion, and rupture of the capsule with demonstrable tumour implants and metastases. This report serves to remind us of the existence of female adnexal tumours of probable Wolffian origin and, in particular, their malignant potential.

Maspin expression in CIN 3, microinvasive squamous cell carcinoma, and invasive squamous cell carcinoma of the uterine cervix

Maspin is a serine protease inhibitor with tumor suppression activity. It is expressed in normal breast and prostate tissue but is downregulated or absent in breast and prostate tumors. Recent reports have shown that decreased expression is associated with a greater propensity for metastasis in oral squamous cell carcinomas. We know that some high-grade cervical intraepithelial neoplasia progress to invasive carcinomas while others either persist at the same degree of atypia or regress. The pattern of maspin expression in cervical intraepithelial neoplasia-grade 3, microinvasive squamous carcinomas and overtly invasive squamous cell carcinomas of the uterine cervix was studied to determine the relationship between the extent of maspin expression and the progression of cervical intraepithelial neoplasia to squamous cell carcinoma. In total, 36 cases were evaluated: 18 cases of cervical intraepithelial neoplasia-grade 3, seven cases of microinvasive squamous cell carcinoma and 11 cases of invasive squamous cell carcinoma. A monoclonal antibody was used on paraffin-embedded tissues. Immunoreactivity was scored semiquantitatively using a scale of 0–3. The sums of the scores of the different groups were compared using the Mann–Whitney U-test. A significant decrease in maspin scores was noted between cervical intraepithelial neoplasia-grade 3 vs invasive squamous cell carcinoma (P<0.005), microinvasive squamous cell carcinoma vs invasive squamous cell carcinoma (P<0.05), and cervical intraepithelial neoplasia-grade 3 vs tumor emboli (P<0.005). Although not statistically significant, scores of cervical intraepithelial neoplasia-grade 3 associated with invasive squamous cell carcinoma were lower compared to that cervical intraepithelial neoplasia-grade 3 without invasive squamous cell carcinoma. These findings suggest that maspin likely plays a role in disease progression from in situ to invasive carcinoma. Virtual absence of maspin immunopositivity in tumor emboli indicates that maspin may also play a role in metastasis.

The expression of selenium-binding protein 1 is decreased in uterine leiomyoma

BackgroundSelenium has been shown to inhibit cancer development and growth through the mediation of selenium-binding proteins. Decreased expression of selenium-binding protein 1 has been reported in cancers of the prostate, stomach, colon, and lungs. No information, however, is available concerning the roles of selenium-binding protein 1 in uterine leiomyoma.MethodsUsing Western Blot analysis and immunohistochemistry, we examined the expression of selenium-binding protein 1 in uterine leiomyoma and normal myometrium in 20 patients who had undergone hysterectomy for uterine leiomyoma.Results and DiscussionThe patient age ranged from 34 to 58 years with a mean of 44.3 years. Proliferative endometrium was seen in 8 patients, secretory endometrium in 7 patients, and atrophic endometrium in 5 patients. Two patients showed solitary leiomyoma, and eighteen patients revealed 2 to 5 tumors. Tumor size ranged from 1 to 15.5 cm with a mean of 4.3 cm. Both Western Blot analysis and immunohistochemistry showed a significant lower level of selenium-binding protein 1 in leiomyoma than in normal myometrium. Larger tumors had a tendency to show a lower level of selenium-binding protein 1 than smaller ones, but the difference did not reach a statistical significance. The expression of selenium-binding protein 1 was the same among patients with proliferative, secretory, and atrophic endometrium in either leiomyoma or normal myometrium. Also, we did not find a difference of selenium-binding protein 1 level between patients younger than 45 years and older patients in either leiomyoma or normal myometrium.ConclusionsDecreased expression of selenium-binding protein 1 in uterine leiomyoma may indicate a role of the protein in tumorigenesis. Our findings may provide a basis for future studies concerning the molecular mechanisms of selenium-binding protein 1 in tumorigenesis as well as the possible use of selenium in prevention and treatment of uterine leiomyoma.

High-grade serous carcinoma arising in a low-grade serous carcinoma and micropapillary serous borderline tumour of the ovary in a 23-year-old woman.

but so far no data about this transcriptional factor have been published for malignant plasma cells. FOXP1 is considered a potential therapeutic target in a variety of cancers. Koon et al. wrote a review in 2007 about FOXP1 changes in gastrointestinal, lung, head, neck and breast cancer, genitourinary malignancies and B-cell lymphomas. They stated that FOXP1-directed therapy could have significant potential, but that many data about FOXP1 function are still missing. It is still not clear whether FOXP1 acts as an oncogene or tumour suppressor, or if there are other, as yet uninvestigated malignancies in which it has prognostic value. Our data describe a case of MM with hyperploidy, multiple IgH translocations and FOXP1 expression; to our knowledge this is the first reported case with six translocated genes as well as the first reported case of FOXP1 expression in malignant plasma cells. It demonstrates the need for further investigation into the prognostic value of FOXP1 protein expression in MM.

High Nuclear Grade, Frequent Mitotic Activity, Cyclin D1 and p53 Overexpression Are Associated with Stromal Invasion in Mammary Intracystic Papillary Carcinoma

Abstract:  Stromal invasion is identified with difficulty in routine hematoxylin‐eosin‐stained sections of core needle biopsy specimens from mammary intracystic papillary carcinomas. The goal of this study was to determine if nuclear grade, mitotic activity, and immunohistochemical stains for p53 and cyclin D1 would assist in differentiating intracystic papillary carcinomas without stromal invasion (ICPC) from tumors with stromal invasion (ICPC‐INVA). Eight cases of ICPC and 12 cases of ICPC‐INVA were reviewed. Hematoxylin‐eosin slides were examined to determine the histologic features. Immunohistochemistry was performed using monoclonal antibodies to human p53 and cyclin D1. Fishers exact test was used to compare the nuclear grade, mitotic activity, and immunoreactivity between ICPC and ICPC‐INVA. High nuclear grade was more often associated with ICPC‐INVA than with ICPC, although the difference was not statistically significant (p = 0.069). Frequent mitotic activity was associated with ICPC‐INVA more than with ICPC (p = 0.0198). All cases of ICPC were negative for either p53 or cyclin D1, whereas 7 of 12 cases (58.3%) of ICPC‐INVA were positive for either cyclin D1 alone (3 cases), p53 alone (3 cases), or both cyclin D1 and p53 (1 case) (p = 0.0147). Identical nuclear grade, mitotic activity, and immunostaining patterns were seen in the intracystic and the invasive components, and in the core biopsy and the excision of the same tumor. When any one of the positive indicators (high nuclear grade, frequent mitotic activity, or positive immunostains for cyclin D1 and/or p53) was present, the positive predictive value for stromal invasion was 91.7%. When none of the positive indicators was present, the negative predictive value was 87.5%. 

Prevalence, distribution, and viral burden of all 15 high-risk human papillomavirus types in adenosquamous carcinoma of the uterine cervix: a multiplex real-time polymerase chain reaction–based study

Human papillomavirus (HPV) 16 and 18 are the types most commonly found in cervical adenosquamous carcinoma. Multiple HPV types have been found in cervical adenocarcinoma but not in the adenosquamous variant. Type-specific detection of high-risk (HR) HPV allows the detection of co-infection by multiple HPV types and assessment of viral load per cell. Our aim was to identify and quantify all HR HPV types in cervical adenosquamous carcinoma and to correlate viral loads with prognosis-related histologic features. All 15 HR HPV types were tested for by multiplex real-time polymerase chain reaction, and standard curves were created for each type. Viral loads were determined retrospectively. Prognosis-related histologic features were correlated with specific HPV types and the viral loads. A total of 80% of the tumors examined expressed HPV. Types 16/18 were detected in 86% of these cases, whereas the remaining 14% of the positive cases were infected by other types. A single type of virus was detected in 67% of cases, 2 in 29%, and 3 in 4%. Poor prognostic features were seen in 84.6% of the tumors infected with HPV 16, 46% of those infected with HPV 18, and 100% of those infected with other types. As expected, HPV 16, HPV 18, or both were the most frequent viral types; HPV 73 was the next most frequent type. Multiple HPV types were detected in 33% of the tumors. Non-HPV 16/18 cases had low viral loads, but all of these had poor prognosis-related histologic features. Two of the three recurrent cases had multiple viral types.

Progressive loss of selenium-binding protein 1 expression correlates with increasing epithelial proliferation and papillary complexity in ovarian serous borderline tumor and low-grade serous carcinoma

Ovarian serous borderline tumor, micropapillary serous borderline tumor, and low-grade serous carcinoma often show a spectrum of histologic components with increasing epithelial proliferation and papillary complexity from flat cyst wall, hierarchical structures (with primary papillae branching into secondary papillae), micropapillae, and invasive carcinoma. Although tremendous research has been carried out to elucidate the causes of these tumors, the pathogenesis remains unclear. Literature has described a relationship between insufficient selenium intake and increased risk of cancer. The anticancer action of selenium has been suggested to be mediated by selenium-binding protein 1 as selenium-binding protein 1 is decreased in several cancers. The aim of the study was to examine by immunohistochemistry the expression of selenium-binding protein 1 in the various histologic components within ovarian serous borderline tumor, micropapillary serous borderline tumor, and low-grade serous carcinoma. Our study consisted of 62 cases of ovarian serous borderline tumor, 11 of micropapillary serous borderline tumor, and 7 of low-grade serous carcinoma. Review of archival slides showed flat cyst wall in 69 cases, primary and secondary papillae of hierarchical structures in 75 cases, micropapillae in 26 cases, microinvasion in 1 case, and frankly invasive carcinoma in 7 cases. The strongest immunoreactivity of selenium-binding protein 1 was seen in epithelial cells of flat cyst wall and primary papillae, followed by secondary papillae of the hierarchical structures. Micropapillae and invasive carcinoma (including microinvasion) exhibited a near complete loss of selenium-binding protein 1 expression. Selenium-binding protein 1 immunoreactivity remained the same regardless of the size of the micropapillae. Similar selenium-binding protein 1 expression was seen in the same histologic components from either ovarian serous borderline tumor or micropapillary serous borderline tumor. The gradual loss of selenium-binding protein 1 associated with increasing epithelial proliferation and papillary complexity indicates that selenium-binding protein 1 is involved in tumorigenesis of ovarian serous borderline tumor, micropapillary serous borderline tumor, and low-grade serous carcinoma. Our findings may provide a basis for future studies concerning the molecular mechanisms of selenium-binding protein 1 in tumorigenesis as well as a possible role of selenium in chemoprevention and treatment of ovarian serous borderline tumor, micropapillary serous borderline tumor, and low-grade serous carcinoma.

Ewing’s Sarcoma / Peripheral Primitive Neuroectodermal Tumor (ES/PNET) Differentiation in Endometrial Serous Carcinomas

The association of Ewings sarcoma/peripheral neuroectodermal tumor and endometrioid type endometrial carcinoma has been reported relatively recently. We have recently identified Ewings sarcoma/peripheral neuroectodermal tumor differentiation in uterine serous carcinomas and undertook this study to evaluate the frequency of both serous and endometrioid carcinomas expressing Ewings sarcoma/peripheral neuroectodermal tumor differentiation. Seventy cases of uterine serous carcinoma were retrieved from the archival files and stained with antibodies to CD99. Positive and negative control slides were run with each staining batch. Perinuclear dot-like and/or membranous staining was regarded as positive. The frequency of Ewings sarcoma/peripheral neuroectodermal tumor differentiation in 56 FIGO grade 3 endometrioid carcinomas was also determined and 7% uterine serous and 12.5% of FIGO grade 3 endometrioid endometrial carcinomas showed Ewings sarcoma/peripheral neuroectodermal tumor differentiation. Given the worse prognosis associated with Ewings sarcoma/peripheral neuroectodermal tumor differentiation, even in neoplasms already at high risk for recurrence and metastasis, a high index of suspicion for Ewings sarcoma/peripheral neuroectodermal tumor should be maintained in high-grade uterine serous carcinomas.